This product is no longer sold by Raintree Nutrition, Inc. See the main product page for more information on why. Click on one of the product search links in the left margin of this page to find other available products. You can also see the rainforest products page to find other companies selling rainforest herbal supplements or rainforest plants in general.
N-TENSE Topical combines the rainforest's most potent and powerful plants into one synergistic formula for topical use on the skin. These power plants have been independently documented around the world with anticancerous actions.* More information can also be found in the new Anti-Cancerous Guide
Ingredients: A herbal blend of sangre de grado, copaiba, graviola, espinheira santa, suma, pau d'arco, mullaca, vassourinha, and mutamba extracted in distilled water and alcohol. To prepare this natural remedy yourself: combine equal parts of graviola, espinheira santa, suma, pau d'arco, mullaca, vassourinha, and mutamba and make a tincture following the instructions on the Methods of Preparing Herbal Remedies page. To make a small amount... 1 part could be a tablespoon (you'd have 7 tablespoon of the blended herbal formula). Once the tincture is finished, measure it. For every 4 parts of the finished tincture, add one part sangre de grado resin and one part copaiba oil. Mix together and bottle it in a dark glass bottle (it will naturally separate... just shake well before using).Suggested Use: Shake well and apply directly on the skin several times daily. Allow to dry completely before covering with clothing.
Sangre de Grado (Croton lechleri)
Alonso-Castro, A., et al. "Rutin exerts antitumor effects on nude mice bearing SW480 tumor."
Arch. Med. Res. 2013 Jul; 44(5): 346-51.
Castelli, S., et al. "A natural anticancer agent taspine targets human topoisomerase IB." Anticancer Agents Med. Chem. 2013 Feb; 13(2): 356-63.
Montopoli, M., et al. "Croton lechleri sap and isolated alkaloid taspine exhibit inhibition against human melanoma SK23 and colon cancer HT29 cell lines." J. Ethnopharmacol. 2012 Dec 18; 144(3): 747-53.
Zhang, Y., et al. "Antitumor activity of taspine by modulating the EGFR signaling pathway of Erk1/2 and Akt in vitro and in vivo." Planta Med. 2011 Nov;77(16):1774-81.
Alonso-Castro, A., et al. "Antitumor effect of Croton lechleri Mull. Arg. (Euphorbiaceae). J Ethnopharmacol. 2012 Mar; 140(2): 438-42.
Lu, W., et al. "A novel taspine analog, HMQ1611, inhibits growth of non-small cell lung cancer by inhibiting angiogenesis." Oncol. Lett. 2012 Nov; 4(5): 1109-1113.
Zhang, Y., et al. "A novel angiogenesis inhibitor impairs LoVo cell survival via targeting against human VEGFR and its signaling pathway of phosphorylation." Cell Death Dis. 2012 Oct 11; 3: e406. (LoVo cells are human colon cancer cells)
He, H., et al. "Tas13D inhibits growth of SMMC-7721 cell via suppression VEGF and EGF expression." Asian Pac. J. Cancer Prev. 2012; 13(5): 2009-14.
Zhang, Y., et al. "Facile synthesis and biological evaluation of novel symmetrical biphenyls as antitumor agents." Med Chem. 2012 Mar; 8(2): 145-50.
Zhang, Y., et al. "Effects of taspine on proliferation and apoptosis by regulating caspase-3 expression and the ratio of Bax/Bcl-2 in A431 cells." Phytother Res. 2011 Mar; 25(3): 357-64. (A431 cells are squamous cell skin cancer)
Zhan, Y., et al. "Activity of taspine isolated from Radix et Rhizoma Leonticis against estrogen-receptor-positive breast cancer." Fitoterapia. 2011 Sep; 82(6): 896-902.
Takami, Y., et al. "Proanthocyanidin derived from the leaves of Vaccinium virgatum suppresses platelet-derived growth factor-induced proliferation of the human hepatic stellate cell line LI90." Hepatol Res. 2010 Apr; 40(4): 337-45.
Fayed, W., et al. "Identification of a novel topoisomerase inhibitor effective in cells overexpressing drug efflux transporters." PLoS One. 2009 Oct; 4(10): e7238.
Zhang, Y., et al. "[Inhibitory effect of taspine on mouse S180 sarcoma and its mechanism]." Zhongguo Zhong Yao Za Zhi. 2007 May; 32(10) :953-6.
Gonzales, G., et al. "Medicinal plants from Peru: a review of plants as potential agents against cancer." Anticancer Agents Med, Chem. 2006 Sep; 6(5) :429-44.
Rossi, D., et al. "Evaluation of the mutagenic, antimutagenic and antiproliferative potential of Croton lechleri (Muell. Arg.) latex." Phytomedicine. 2003 Mar; 10(2-3): 139-44.
Sandoval, M., et al. "Sangre de grado (Croton palanostigma) induces apoptosis in human gastrointestinal cancer cells." J. Ethnopharmacol. 2002; 80(2-3): 121-9.
Chen, Z., et al. "Studies on the anti-tumour, anti-bacterial, and wound-healing properties of dragon’s blood." Planta Med. 1994; 60(6): 541-45.
Pieters, L., et al. "Isolation of a dihydrobenzofuran lignan from South American dragon’s blood (Croton sp.) as an inhibitor of cell proliferation." J. Nat. Prod. 1993; 56(6): 899-906.
Itokawa, H., et al. "A cytotoxic substance from sangre de grado." Chem. Pharm. Bull. 1991; 39(4): 1041-42.
Copaiba Resin (Copaifera sp.)
Copaiba oil and several of it's active chemicals have demonstrated good actions against cancer in the following research studies.*
Di Sotto, A., "New insights in the antitumor effects of β-caryophyllene in breast cancer cells: The role of cannabinoid and adrenergic systems." Annals of Oncology. 2018 Mar; 29(3): 94.
Fidyt, K., et al. "β-caryophyllene and β-caryophyllene oxide—natural compounds of anticancer and analgesic properties." Cancer Med. 2016 Oct; 5(10): 3007–3017.
Abrão, F., et al. "Copaifera langsdorffii oleoresin and its isolated compounds: antibacterial effect and antiproliferative activity in cancer cell lines." BMC Complement. Altern. Med. 2015 Dec 21; 15: 443.
Jung, J., et al. "β-Caryophyllene potently inhibits solid tumor growth and lymph node metastasis of B16F10 melanoma cells in high-fat diet-induced obese C57BL/6N mice." Carcinogenesis. 2015 Sep; 36(9): 1028-39.
Botelho, N., et al. "Immunohistochemistry of the uterine cervix of rats bearing the Walker 256 tumor treated with copaiba balsam." Acta Cir. Bras. 2013 Mar; 28(3): 185-9.
dos Santos Junior, H., et al. "Evaluation of native and exotic Brazilian plants for anticancer activity." J Nat Med. 2010 Apr; 64(2): 231-8.
Tundis, R., et al. "In vitro cytotoxic effects of Senecio stabianus Lacaita (Asteraceae) on human cancer cell lines." Nat. Prod. Res. 2009; 23(18): 1707-18.
Gomes, M., et al. "Antineoplasic activity of Copaifera multijuga oil and fractions against ascitic and solid Ehrlich tumor." J. Ethnopharmacol. 2008 Sep; 119(1): 179-84.
Legault, J., et al. "Potentiating effect of beta-caryophyllene on anticancer activity of alpha-humulene, isocaryophyllene and paclitaxel." J. Pharm. Pharmacol. 2007 Dec; 59(12): 1643-7.
Cavalcanti, B. C., et al. "Genotoxicity evaluation of kaurenoic acid, a bioactive diterpenoid present in Copaiba oil." Food Chem. Toxicol. 2006; 44(3): 388-92.
Krauchenco, S., et al. "Three-dimensional structure of an unusual Kunitz (STI) type trypsin inhibitor from Copaifera langsdorffii." Biochimie. 2004; 86(3): 167-72.
Legault, J., et al. "Potentiating effect of beta-caryophyllene on anticancer activity of alpha-humulene, isocaryophyllene and paclitaxel." J. Pharm. Pharmacol. 2007 Dec; 59(12): 1643-7.
Lima, S. R., et al. "In vivo and in vitro studies on the anticancer activity of Copaifera multijuga Hayne and its fractions." Phytother. Res. 2003 Nov; 17(9): 1048-53.
Costa-Lotufo, L. V., et al. "The cytotoxic and embryotoxic effects of kaurenoic acid, a diterpene isolated from Copaifera langsdorffi." Toxicon. 2002; 40(8): 1231-34.
de Almeida Alves, T. M., et al. "Biological screening of Brazilian medicinal plants."Mem. Inst. Oswaldo Cruz 2000; 95(3): 367-73.
Ohsaki, A., et al. "The isolation and in vivo potent antitumor activity of clerodane diterpenoids from the oleoresin of Brazilian medicinal plant Copaifera langsdorfii Desfon." Bioorg. Med. Chem. Lett. 1994; 4: 2889-92.
Graviola (Annona muricata)
Graviola contains over 100 Annonaceous acetogenins which have shown in laboratory studies to be selectively cytotoxic to cancer cells without toxicity to healthy cells. Many published studies report that these acetogenins have demonstrated selective cytotoxicity to tumor cells with as little as 1 part per million.
Indrawati, L., et al. "The effect of an Annona muricata leaf extract on nutritional status and cytotoxicity in colorectal cancer: a randomized controlled trial." Asia Pac. J. Clin. Nutr. 2017; 26(4): 606-612. [Free full article]
Rady, I., et al. “Anticancer properties of graviola (Annona muricata): A comprehensive mechanistic review.” Oxid. Med. Cell. Longev. 2018 Jul; 2018: 1826170. [Free PMC Article]
Quílez, A., et al. “Potential therapeutic applications of the genus Annona: Local and traditional uses and pharmacology.” J. Ethnopharmacol. 2018 Oct; 225: 244-270.
Yajid, A. et al. “Potential Benefits of Annona muricata in Combating Cancer: A Review. Malays. J. Med. Sci. 2018 Feb; 25(1): 5-15. [PMC free article]
Qazi, A., et al. “Emerging therapeutic potential of graviola and its constituents in cancers.” Carcinogenesis. 2018 Apr; 39(4): 522-533.
Gavamukulya, Y., et al. “Annona muricata: Is the natural therapy to most disease conditions including cancer growing in our backyard? A systematic review of its research history and future prospects.” Asian Pac. J. Trop. Med. 2017 Sept; 10(9): 835-848 [ScienceDirect free article]
Moghadamtousi, S., et al. “Annona muricata (Annonaceae): A review of its traditional uses, isolated acetogenins and biological activities.” Int. J. Mol. Sci. 2015 Jul; 16(7): 15625-58. [PMC Free article]
Mangal, M., et al. “Acetogenins as Potential Anticancer Agents.” Anticancer Agents Med. Chem. 2015; 16(2): 138-59.
Ma, C., et al. “Non-targeted metabolomic analysis on multidrug resistance hepatocellular carcinoma cell and reversal effect of annonaceous acetogenins.” J. Pharm. Biomed. Anal. 2019 Feb; 164: 489-495. Sabapati, M., et al. "Solid lipid nanoparticles of Annona muricata fruit extract: formulation, optimization and in vitro cytotoxicity studies." Drug Dev. Ind. Pharm. 2019 Jan 19:1-10.
Torres, C., Effect of Morinda citrifolia and Annona muricata on Erhlich tumor cells in Swiss albino mice and in vitro fibroblast cells." J. Med. Food. 2019 Jan; 22(1): 46-51.
Kim, J., "Annona muricata leaf extract triggered intrinsic apoptotic pathway to attenuate cancerous features of triple negative breast cancer MDA-MB-231." Cells. Evid. Based Complement. Alternat. Med. 2018 Jul; 2018: 7972916.
Rady, I., et al. "Anticancer properties of graviola (Annona muricata): A comprehensive mechanistic review." Oxid. Med. Cell Longev. 2018 Jul; 2018: 1826170.
Sánchez-Navarro, M., et al. "Cytotoxic and bactericidal effect of silver nanoparticles obtained by green synthesis method using Annona muricata aqueous extract and functionalized with 5-Fluorouracil." Bioinorg. Chem. Appl. 2018 Oct; 2018: 6506381.
Moreau, D., et al. "[Self medication with Annona muricata L. (corossol) as an anti-cancer agent in Reunion]." Rev. Mal. Respir. 2018 Nov; 35(9): 948-955.
Abdul Wahab, S., et at. "Exploring the leaves of Annona muricata L. as a source of potential anti-inflammatory and anticancer agents." Front. Pharmacol. 2018 Jun; 9: 661.
Chamcheu, J., "Graviola (Annona muricata) exerts anti-proliferative, anti-clonogenic and pro-apoptotic effects in human non-melanoma skin cancer UW-BCC1 and A431 cells in vitro: involvement of hedgehog signaling." Int. J. Mol. Sci. 2018 Jun; 19(6).
Dawood, H., "Integrated in silico-in vitro strategy for screening of some traditional Egyptian plants for human aromatase inhibitors." J. Ethnopharmacol. 2018 Oct; 224: 359-372.
Rosdi, M., et al. "Molecular docking studies of bioactive compounds from Annona muricata Linn as potential inhibitors for Bcl-2, Bcl-w and Mcl-1 antiapoptotic proteins." Apoptosis. 2018 Jan; 23(1): 27-40.
Ma, C., et al. “Metabolomics analysis of the potential anticancer mechanism of annonaceous acetogenins on a multidrug resistant mammary adenocarcinoma cell.” Anal. Biochem. 2018 Jul 15; 553: 1-6.
Roduan, M., "Annona muricata leaves extracts prevent DMBA/TPA-induced skin tumorigenesis via modulating antioxidants enzymes system in ICR mice." Biomed. Pharmacother. 2017 Oct; 94: 481-488.
Abdullah, M., et al. "The value of caspase-3 after the application of Annona muricata leaf extract in COLO-205 colorectal cancer cell line." Gastroenterol. Res. Pract. 2017; 2017: 4357165.
Morosetti, G., "Ellagic acid and Annona muricata in the chemoprevention of HPV-related pre-neoplastic lesions of the cervix." Oncol Lett. 2017 Mar; 13(3): 1880-1884.
Yap, C. et al. "Annonacin exerts antitumor activity through induction of apoptosis and extracellular signal-regulated kinase inhibition." Pharmacognosy Res. 2017 Oct-Dec; 9(4): 378-383.
Foster, K., et al. "Reliance on medicinal plant therapy among cancer patients in Jamaica." Cancer Causes Control. 2017 Nov; 28(11): 1349-1356.
Tundis, R., "Annona species (Annonaceae): a rich source of potential antitumor agents? Ann. N. Y Acad Sci. 2017 Jun; 1398(1): 30-36.
Prabhakaran, K., et al. "Polyketide natural products, acetogenins from graviola (Annona muricata L), its biochemical, cytotoxic activity and various analyses through computational and bio-programming methods." Curr. Pharm. Des. 2016; 22(34): 5204-5210.
Sun, L., et al. "Isolation of three new Anonaceous acetogenins from graviola fruit (Annona muricata) and their anti-proliferation on human prostate cancer cell PC-3." Bioorg. Med. Chem. Lett. 2016 Sep; 26(17): 4382-5.
Clement, Y., et al. "Herbal remedies and functional foods used by cancer patients attending specialty oncology clinics in Trinidad." BMC Complement. Altern. Med. 2016 Oct; 16(1): 399
Kuete, V., et al. "Cytotoxicity of methanol extracts of Annona muricata, Passiflora edulis and nine other Cameroonian medicinal plants towards multi-factorial drug-resistant cancer cell lines. Springerplus. 2016 Sep; 5(1): 1666.
Najmuddin, S., et al. "Anti-cancer effect of Annona muricata Linn leaves crude extract (AMCE) on breast cancer cell line." BMC Complement. Altern. Med. 2016 Aug; 16(1): 311.
Prabhakaran, K., "Polyketide natural products, acetogenins from graviola (Annona muricata L), its biochemical, cytotoxic activity and various analyses through computational and bio-programming methods." Curr. Pharm. Des. 2016; 22(34): 5204-5210.
Liu, N., et al. "Functional proteomic analysis reveals that the ethanol extract of Annona muricata L. induces liver cancer cell apoptosis through endoplasmic reticulum stress pathway." J. Ethnopharmacol. 2016 Aug; 189: 210-7.
Antony, P., and Vijayan, R. "Acetogenins from Annona muricata as potential inhibitors of antiapoptotic proteins: a molecular modeling study." Drug Des. Devel. Ther. 2016 Apr; 10: 1399-410.
Shi, Y., et al. "[Structure activity relationship of annonaceous acetogenins against multidrug resistant human lung cancer cell line A549/Taxol in vitro]." Zhongguo Zhong Yao Za Zhi. 2016 May; 41(10): 1884-1888.
Liaw, C., et al. “Acetogenins from Annonaceae.” Prog. Chem. Org. Nat. Prod. 2016; 101: 113-230.
Qian, J., et al. “Annonaceous acetogenins reverses drug resistance of human hepatocellular carcinoma BEL-7402/5-FU and HepG2/ADM cell lines.” Int. J. Clin. Exp. Pathol. 2015 Sep; 8(9): 11934-44.
Magadi, V. "Evaluation of cytotoxicity of aqueous extract of graviola leaves on squamous cell carcinoma cell-25 cell lines by 3-(4,5-dimethylthiazol-2-Yl) -2,5-diphenyltetrazolium bromide assay and determination of percentage of cell inhibition at G2M phase of cell cycle by flow cytometry: An in vitro study." Contemp. Clin. Dent. 2015 Oct-Dec; 6(4): 529-33.
Yang, C., et al. "Synergistic interactions among flavonoids and acetogenins in graviola (Annona muricata) leaves confer protection against prostate cancer." Carcinogenesis. 2015 Jun; 36(6): 656-65.
Zorofchian, S., et al. "The chemopotential effect of Annona muricata leaves against azoxymethane-induced colonic aberrant crypt foci in rats and the apoptotic effect of acetogenin annomuricin E in HT-29 cells: a bioassay-guided approach." PLoS One. 2015 Apr; 10(4): e0122288.
Asare, G., et al. "Antiproliferative activity of aqueous leaf extract of Annona muricata L. on the prostate, BPH-1 cells, and some target genes." Integr. Cancer Ther. 2015 Jan; 14(1): 65-74.
Yuan, F., et al. “Structure-activity relationships of diverse ACGs against multidrug resistant human lung cancer cell line A549/Taxol.” Bioorg. Med. Chem. Lett. 2015 Feb; 25(4): 787-90.
Pieme, C., et al. "Antiproliferative activity and induction of apoptosis by Annona muricata (Annonaceae) extract on human cancer cells." BMC Complement. Altern. Med. 2014 Dec; 14: 516.
Gavamukulya, Y., et al. "Phytochemical screening, anti-oxidant activity and in vitro anticancer potential of ethanolic and water leaves extracts of Annona muricata (Graviola)." Asian Pac. J. Trop. Med. 2014 Sep; 7S1: S355-63.
Zorofchian, M., et al. "Annona muricata leaves induce G1 cell cycle arrest and apoptosis through mitochondria-mediated pathway in human HCT-116 and HT-29 colon cancer cells." J. Ethnopharmacol. 2014 Oct; 156: 277-89.
Moghadamtousi, S., et al. "Annona muricata leaves induced apoptosis in A549 cells through mitochondrial-mediated pathway and involvement of NF-κB." BMC Complement. Altern. Med. 2014 Aug; 14: 299.
Sun, S., et al. "Three new anti-proliferative Annonaceous acetogenins with mono-tetrahydrofuran ring from graviola fruit (Annona muricata)." Bioorg. Med. Chem. Lett. 2014 Jun; 24(12): 2773-6.
Paul, J., et al. "Anti cancer activity on graviola, an exciting medicinal plant extract vs various cancer cell lines and a detailed computational study on its potent anti-cancerous leads." Curr. Top. Med. Chem. 2013; 13(14): 1666-73.
de Pedro, N., et al. "Mitochondrial complex I inhibitors, acetogenins, induce HepG2 cell death through the induction of the complete apoptotic mitochondrial pathway." J. Bioenerg. Biomembr. 2013 Feb; 45(1-2): 153-64.
de Pedro, N., et al. "Analysis of cytotoxic activity at short incubation times reveals profound differences among Annonaceus acetogenins, inhibitors of mitochondrial Complex I." J. Bioenerg Biomembr. 2013 Feb; 45(1-2): 145-52
Hamizah, S., et al. "Chemopreventive potential of Annona muricata L leaves on chemically-induced skin papillomagenesis in mice." Asian Pac. J. Cancer Prev. 2012; 13(6): 2533-9.
Torres, M., et al. "Graviola: a novel promising natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo through altering cell metabolism." Cancer Lett. 2012 Oct; 323(1): 29-40.
Chen, Y., et al. "Anti-tumor activity of Annona squamosa seeds extract containing Annonaceous acetogenin compounds." J. Ethnopharmacol. 2012 Jul; 142(2): 462-6.
Chen, Y., et al. "Antitumor activity of Annonaceous acetogenins in HepS and S180 xenografts bearing mice." Bioorg. Med. Chem. Lett. 2012 Apr; 22(8): 2717-9.
George, V., et al. "Quantitative assessment of the relative antineoplastic potential of the n-butanolic leaf extract of Annona muricata Linn. in normal and immortalized human cell lines." Asian Pac. J. Cancer Prev. 2012; 13(2) :699-704.
Gomes de Melo, J., et al. "Antiproliferative activity, antioxidant capacity and tannin content in plants of semi-arid northeastern Brazil." Molecules. 2010 Nov; 15(12): 8534-42.
Ko, Y., et al. "Annonacin induces cell cycle-dependent growth arrest and apoptosis in estrogen receptor-a-related pathways in MCF-7 cells." J. Ethnopharmacol. 2011 Oct; 137(3): 1283-90.
Tantithanaporn, S., et al. "Cytotoxic activity of acetogenins and styryl lactones isolated from Goniothalamus undulatus Ridl. root extracts against a lung cancer cell line (COR-L23)." Phytomedicine. 2011 Apr; 18(6): 486-90.
Coothankandaswamy, V., et al. "The alternative medicine pawpaw and its acetogenin constituents suppress tumor angiogenesis via the HIF-1/VEGF pathway." J. Nat. Prod. 2010 May; 73(5): 956-61.
Yang, h., et al. "Structure-activity relationships of diverse Annonaceous acetogenins against human tumor cells." Bioorg Med Chem Lett. 2009 Apr; 19(8): 2199-202.
Kojima, N. "Systematic synthesis of antitumor Annonaceous acetogenins." Yakugaku Zasshi. 2004; 124(10): 673-81.
Tormo, J., et al. "In vitro antitumor structure-activity relationships of threo/trans/threo mono-tetrahydro-furanic acetogenins: Correlations with their inhibition of mitochondrial complex I." Oncol. Res. 2003; 14(3): 147-54.
Yuan, S., et al. "Annonacin, a mono-tetrahydrofuran acetogenin, arrests cancer cells at the G1 phase and causes cytotoxicity in a Bax- and caspase-3-related pathway." Life Sci. 2003 May: 72(25): 2853-61.
Liaw, C., et al. "New cytotoxic monotetrahydrofuran Annonaceous acetogenins from Annona muricata." J. Nat. Prod. 2002; 65(4): 470-75
Gonzalez-Coloma, A., et al. "Selective action of acetogenin mitochondrial complex I inhibitors." Z. Naturforsch. 2002; 57(11-12): 1028-34.
Chang, F., et al. "Novel cytotoxic Annonaceous acetogenins from Annona muricata." J. Nat. Prod. 2001; 64(7): 925-31.
Jaramillo, M., et al. "Cytotoxicity and antileishmanial activity of Annona muricata pericarp." Fitoterapia. 2000; 71 (2): 183-6.
Betancur-Galvis, L., et al. "Antitumor and antiviral activity of Colombian medicinal plant extracts." Mem. Inst. Oswaldo Cruz. 1999; 94(4): 531-35.
Kim, G., et al. "Muricoreacin and murihexocin C, mono-tetrahydrofuran acetogenins, from the leaves of Annona muricata." Phytochemistry. 1998; 49(2): 565-71.
Kim, G., et al. "Two new mono-tetrahydrofuran ring acetogenins, annomuricin E and muricapentocin, from the leaves of Annona muricata." J. Nat. Prod. 1998; 61(4): 432-36.
Nicolas, H., et al. "Structure-activity relationships of diverse Annonaceous acetogenins against multidrug resistant human mammary adenocarcinoma (MCF-7/Adr) cells." J. Med. Chem. 1997; 40(13): 2102-6.
Zeng, L., et al. "Five new monotetrahydrofuran ring acetogenins from the leaves of Annona muricata." J. Nat. Prod. 1996; 59(11): 1035-42.
Wu, F., et al. "Two new cytotoxic monotetrahydrofuran Annonaceous acetogenins, annomuricins A and B, from the leaves of Annona muricata." J. Nat. Prod. 1995; 58(6): 830-36.
Oberlies, N., et al. "Tumor cell growth inhibition by several Annonaceous acetogenins in an in vitro disk diffusion assay." Cancer Lett. 1995; 96(1): 55-62.
Wu, F., et al. "Additional bioactive acetogenins, annomutacin and (2,4-trans and cis)-10R-annonacin-A-ones, from the leaves of Annona muricata." J. Nat. Prod. 1995; 58(9): 1430-37.
Wu, F., et al. "New bioactive monotetrahydrofuran Annonaceous acetogenins, annomuricin C and muricatocin C, from the leaves of Annona muricata." J. Nat. Prod. 1995; 58(6): 909-5.
Wu, F., et al. "Muricatocins A and B, two new bioactive monotetrahydrofuran Annonaceous acetogenins from the leaves of Annona muricata." J. Nat. Prod. 1995; 58(6): 902-8.
Sundarrao, K., et al. "Preliminary screening of antibacterial and antitumor activities of Papua New Guinean native medicinal plants." Int. J. Pharmacog. 1993; 31(1): 3-6.
Suma (Pfaffia paniculata)
Suma contains novel saponins called pfaffosides which have been documented to inhibit melanoma in vitro in laboratory studies.* In other research, suma demonstrated other anticancerous and antitumorous actions.*
Almeida, I., et al. "In vivo antimutagenic activity of the medicinal plants Pfaffia glomerata (Brazilian ginseng) and Ginkgo biloba." Genet. Mol. Res. 2017 Sep; 16(3).
da Silva, T., C, et al. "Pfaffosidic fraction from Hebanthe paniculata induces cell cycle arrest and caspase-3-induced apoptosis in hepg2 Cells." Evid. Based Complement. Alternat. Med. 2015; 2015: 835796.
Lee, B., et al. "Calenduloside E 6'-methyl ester induces apoptosis in CT-26 mouse colon carcinoma cells and inhibits tumor growth in a CT-26 xenograft animal model." Oncol. Lett. 2012 Jul; 4(1): 22-28.
Nakamura, S., et al. "Brazilian natural medicines. IV. New noroleanane-type triterpene and ecdysterone-type sterol glycosides and melanogenesis inhibitors from the roots of Pfaffia glomerata." Chem. Pharm. Bull. 2010 May; 58(5) :690-5.
da Silva, T., et al. "Pfaffia paniculata (Brazilian ginseng) roots decrease proliferation and increase apoptosis but do not affect cell communication in murine hepatocarcinogenesis." Exp. Toxicol. Pathol. 2010 Mar; 62(2): 145-55.
Nagamine, M., et al. "Cytotoxic effects of butanolic extract from Pfaffia paniculata (Brazilian ginseng) on cultured human breast cancer cell line MCF-7." Exp. Toxicol. Pathol. 2009 Jan; 61(1): 75-82.
Carneiro, C., et al. "Pfaffia paniculata (Brazilian ginseng) methanolic extract reduces angiogenesis in mice." Exp. Toxicol. Pathol. 2007 Aug; 58(6): 427-31.
Matsuzaki, P., et al. "Antineoplastic effects of butanolic residue of Pfaffia paniculata." Cancer Lett. 2006 Jul; 238(1): 85-9.
da Silva, T. C., et al. "Inhibitory effects of Pfaffia paniculata (Brazilian ginseng) on preneoplastic and neoplastic lesions in a mouse hepatocarcinogenesis model." Cancer Lett. 2005 Aug; 226(2): 107-13.
Matsuzaki, P., et al. "Effect of Pfaffia paniculata (Brazilian ginseng) on the Ehrlich tumor in its ascitic form." Life Sci. 2003 Dec; 74(5): 573-9.
Watanabe, T., et al. "Effects of oral administration of Pfaffia paniculata (Brazilian ginseng) on incidence of spontaneous leukemia in AKR/J mice." Cancer Detect. Prev. 2000; 24(2): 173-8.
Takemoto, T., et al. "Pfaffic acids and its derivatives." Japanese patent no 84/10,548. January 20, 1984.
Takemoto, T., et al. "Antitumor pfaffosides from Brazilian carrots." Japanese patent no. 84/184,198. October 19, 1984.
Takemoto, T., et al. "Pfaffic acids and its derivatives." Japanese patent no. (SHO-WA)-118872; 1982. 16 pp.
Nishimoto, N., et al. "Pfaffosides and nortriterpenoid saponins from Pfaffia paniculata" Phytochemistry. 1984; 23(1): 139-42.
Nakai, S., et al. "Pfaffosides. Part 2. Pfaffosides, nortriterpenoid saponins from Pfaffia paniculata." Phytochemistry. 1984; 23(8): 1703-05.
Takemoto, T., et al. "Pfaffic acid, a novel nortriterpene from Pfaffia paniculata Kuntze." Tetrahedron Lett. 1983; 24(10): 1057-60.
Espinheira Santa (Maytenus ilicifolia)
Espinheira santa contains several chemicals with documented anticancerous actions
including maytansine, pristimerin, and maytenin and other triterpene chemicals called
cangorins. The anticancer activities of pristimerin have been illustrated in various cancer cell
lines and animal models in recent research. It has been found to inhibit in vitro and in vivo
proliferation, survival, angiogenesis and metastasis of tumor cells.
Sun, J., et al. "Induction of cell-cycle arrest and apoptosis in human cholangiocarcinoma cells by pristimerin." J. Cell Biochem. 2019 Mar 1.
Cevatemre, B., et al. "A promising natural product, pristimerin, results in cytotoxicity against breast cancer stem cells in vitro and xenografts in vivo through apoptosis and an incomplete autopaghy in breast cancer." Pharmacol. Res. 2018 Mar; 129: 500-514.
Zhang, Y., et al. "Pristimerin enhances the effect of cisplatin by inhibiting the miR 23a/Akt/GSK3β signaling pathway and suppressing autophagy in lung cancer cells." Int. J. Mol. Med. 2019 Mar; 43(3): 1382-1394.
Lee, Y., et al. "Combination of pristimerin and paclitaxel additively induces autophagy in human breast cancer cells via ERK1/2 regulation." Mol. Med. Rep. 2018 Nov; 18(5): 4281-4288.
Tu, Y., et al. "Pristimerin targeting NF-κB pathway inhibits proliferation, migration, and invasion in esophageal squamous cell carcinoma cells." Cell. Biochem. Funct. 2018 Jun; 36(4): 228-240.
Park J., and Kim, J. "Pristimerin, a naturally occurring triterpenoid, attenuates tumorigenesis in experimental colitis-associated colon cancer. Phytomedicine. 2018 Mar; 42: 164-171.
El-Agamy, D., et al. "Pristimerin protects against doxorubicin-induced cardiotoxicity and
fibrosis through modulation of Nrf2 and MAPK/NF-kB signaling pathways." Cancer Manag. Res. 2018 Dec; 11: 47-61.
Mori, Y., et al. "Antitumor effects of pristimerin on human osteosarcoma cells in vitro and in vivo." Onco. Targets Ther. 2017 Nov; 10: 5703-5710.
Zhang, B., et al. "Pristimerin effectively inhibits the malignant phenotypes of uveal melanoma cells by targeting NF κB pathway." Int. J. Oncol. 2017 Sep; 51(3): 887-898.
Yan, Y., et al. "Degradation of P-glycoprotein by pristimerin contributes to overcoming ABCB1-mediated chemotherapeutic drug resistance in vitro." Oncol. Rep. 2017 Jan; 37(1): 31-40.
Yousef, B., et al. "Anticancer potential and molecular targets of pristimerin: A mini- review. Curr. Cancer Drug Targets. 2017; 17(2): 100-108.
Liu, Y., et al. "Anticancer agent pristimerin inhibits IL-2 induced activation of T lymphocytes. J. Exp. Ther. Oncol. 2016 Jul; 11(3): 181-188.
Lee, S., et al. "Anti-cancer effect of pristimerin by inhibition of HIF-1α involves the SPHK-1 pathway in hypoxic prostate cancer cells." BMC Cancer. 2016 Aug; 16: 701.
Xie, G., et al. "Pristimerin overcomes adriamycin resistance in breast cancer cells through suppressing Akt signaling." Oncol. Lett. 2016 May; 11(5): 3111-3116.
Yousef, B., et al. "Pristimerin inhibits proliferation, migration and invasion, and induces apoptosis in HCT-116 colorectal cancer cells." Biomed. Pharmacother. 2016 Apr; 79: 112-9.
Zhao, H., et al. "Pristimerin triggers AIF-dependent programmed necrosis in glioma cells via activation of JNK." Cancer Lett. 2016 Apr; 374(1): 136-148.
Yousef, B., et al. "Pristimerin demonstrates anticancer potential in colorectal cancer cells by inducing G1 phase arrest and apoptosis and suppressing various pro-survival signaling proteins." Oncol. Rep. 2016 Feb; 35(2): 1091-100.
Huang, S., et al. "Pristimerin inhibits prostate cancer bone metastasis by targeting PC-3 stem cell characteristics and VEGF-induced vasculogenesis of BM-EPCs." Cell. Physiol. Biochem. 2015; 37(1): 253-68.
Bukhari, S., et al. "Effects of plants and isolates of Celastraceae family on cancer pathways." Anticancer Agents Med. Chem. 2015; 15(6): 681-93. Review.
Deeb, D., et al. "Inhibition of hTERT/telomerase contributes to the antitumor activity of pristimerin in pancreatic ductal adenocarcinoma cells." Oncol. Rep. 2015 Jul; 34(1): 518-24.
Gao, X., et al. "Anticancer activity of pristimerin in ovarian carcinoma cells is mediated through the inhibition of prosurvival Akt/NF-κB/mTOR signaling." J. Exp. Ther. Oncol. 2014; 10(4): 275-83.
Liu, Y., et al. "Ubiquitin-proteasomal degradation of antiapoptotic survivin facilitates induction of apoptosis in prostate cancer cells by pristimerin." Int. J. Oncol. 2014 Oct; 45(4): 1735-41. Araújo Júnior, R., "Maytenus ilicifolia dry extract protects normal cells, induces apoptosis and regulates Bcl-2 in human cancer cells." Exp. Biol. Med. 2013 Nov; 238(11): 1251-8.
Liu, Y., et al. "Pristimerin induces apoptosis in prostate cancer cells by down-regulating Bcl-2 through ROS-dependent ubiquitin-proteasomal degradation pathway." J. Carcinog. Mutagen. 2013 Nov 5; Suppl 6:005.
Deeb, D., et al. "Pristimerin, a quinonemethide triterpenoid, induces apoptosis in pancreatic cancer cells through the inhibition of pro-survival Akt/NF-κB/mTOR signaling proteins and anti-apoptotic Bcl-2." Int. J. Oncol. 2014 May; 44(5): 1707-15.
Guo, Y., et al. "Triterpenoid pristimerin induced HepG2 cells apoptosis through ROS-mediated mitochondrial dysfunction." J. BUON. 2013 Apr-Jun; 18(2): 477-85.
Yan, Y., et, al. "The triterpenoid pristimerin induces U87 glioma cell apoptosis through reactive oxygen species-mediated mitochondrial dysfunction." Oncol. Lett. 2013 Jan; 5(1): 242-248.
Wang, Y., et al. "Pristimerin causes G1 arrest, induces apoptosis, and enhances the chemosensitivity to gemcitabine in pancreatic cancer cells." PLoS One. 2012; 7(8): e43826.
Mu, X., et al. "Pristimerin inhibits breast cancer cell migration by up- regulating regulator of G protein signaling 4 expression." Asian Pac. J. Cancer Prev. 2012; 13(4): 1097-104.
Mu, X., et al. "Pristimerin, a triterpenoid, inhibits tumor angiogenesis by targeting VEGFR2 activation." Molecules. 2012 Jun; 17(6): 6854-68.
Yadav, V., et al. "Targeting inflammatory pathways by triterpenoids for prevention and treatment of cancer." Toxins (Basel). 2010 Oct; 2(10): 2428-66.
Lu, Z., et al. "Pristimerin induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation by blocking NF-kappaB signaling and depleting Bcr-Abl." Mol. Cancer. 2010 May 19; 9: 112.
Petronelli, A., et al. "Triterpenoids as new promising anticancer drugs." Anticancer Drugs. 2009 Nov; 20(10): 880-92
Byun, J., et al. "Reactive oxygen species-dependent activation of Bax and poly(ADP-ribose) polymerase-1 is required for mitochondrial cell death induced by triterpenoid pristimerin in human cervical cancer cells." Mol Pharmacol. 2009 Oct; 76(4): 734-44.
Tiedemann, R., et al. "Identification of a potent natural triterpenoid inhibitor of proteosome chymotrypsin-like activity and NF-kappaB with antimyeloma activity in vitro and in vivo." Blood. 2009 Apr; 113(17): 4027-37.
Costa, P., et al. "Antiproliferative activity of pristimerin isolated from Maytenus ilicifolia (Celastraceae) in human HL-60 cells." Toxicol In Vitro. 2008 Jun; 22(4): 854-63.
Liu Z, et al. "Metabolism studies of the anti-tumor agent maytansine and its analog ansamitocin P-3 using liquid chromatography/tandem mass spectrometry." J. Mass. Spectrom. 2005; 40(3): 389-99.
Nakao, H., et al. "Cytotoxic activity of maytanprine isolated from Maytenus diversifolia in human leukemia K562 cells." Biol. Pharm. Bull. 2004; 27(8): 1236-40.
Cassady, J. M., et al. "Recent developments in the maytansinoid antitumor agents." Chem. Pharm. Bull. 2004; 52(1): 1-26.
Ohsaki, A., et al. "Four new triterpenoids from Maytenus ilicifolia." J. Nat. Prod. 2004; 67(3): 469-71.
Horn, R. C., et al. "Antimutagenic activity of extracts of natural substances in the Salmonella/microsome assay." Mutagenesis. 2003 Mar; 18(2): 113-8.
Buffa Filho, W., et al. "Quantitative determination for cytotoxic Friedo-nor-oleanane derivatives from five morphological types of Maytenus ilicifolia (Celastraceae) by reverse-phase high-performance liquid chromatography." Phytochem. Anal. 2002 Mar-Apr; 13(2): 75-8.
Miura, N. et al. "Protective effects of triterpene compounds against the cytotoxicity of cadmium in HepG2 cells." Mol. Pharm. 1999; 56(6); 1324-28.
Liu, C., et al. "Eradication of large colon tumor xenografts by targeted delivery of maytansinoids." Proc. Natl. Acad. Sci. 1996 Aug; 93(16): 8618-23.
Shirota, O., et al. "Cytotoxic aromatic triterpenes from Maytenus ilicifolia and Maytenus chuchuhuasca." J. Nat. Prod. 1994; 57(12): 1675-81.
Itokawa, H., et al. "Cangorins F-J, five additional oligo-nicotinated sesquiterpene polyesters from Maytenus ilicifolia." J. Nat. Prod. 1994; 57(4): 460-70.
Arisawa, M., et al. "Cell growth inhibition of KB cells by plant extracts." Natural Med. 1994; 48(4): 338-347.
Itokawa, H., et al. "Oligo-nicotinated sesquiterpene polyesters from Maytenus ilicifolia." J. Nat. Prod. 1993; 56(9); 1479-1485.
Itokawa, H., et al. "Antitumor substances from South American plants." Pharmacobio. Dyn. 1992; 15(1): S
Fox, B. W. "Medicinal plants in tropical medicine. 2. Natural products in cancer treatment from bench to the clinic." Trans. R. Soc. Trop. Med. Hyg. 1991; 85(1): 22-5.
Ravry, M. J., et al. "Phase II evaluation of maytansine (NSC 153858) in advanced cancer. A Southeastern Cancer Study Group trial." Am. J. Clin. Oncol. 1985 Apr; 8(2): 148-50.
Suffnes, M. J., et al. "Current status of the NCI plant and animal product program." J. Nat. Prod. 1982; 45: 1-14.
Cabanillas, F., et al. "Phase I study of maytansine using a 3-day schedule." Cancer Treatment Reports. 1976; (60): 1127-39.
Chabner, B. A., et al. "Initial clinical trials of mayansine, an antitumor plant alkaloid." Cancer Treatment Reports. 1978; (62): 429-33.
O'Connell, M. J., et al. "Phase II trial of maytansine in patients with advanced colorectal carcinoma." Cancer Treatment Reports. 1978 (62); 1237-38.
Wolpert-Defillipes, M. K., et al. "Initial studies on the cytotoxic action of maytansine, a novel ansa macrolide." Biochemical Pharmacology. 1975; 24: 751-54.
Melo, A. M., et al. "First observations on the topical use of primin, plumbagin and maytenin in patients with skin cancer." Rev. Inst. Antibiot. 1974 Dec.
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Pau d'arco (Tabebuia impetiginosa)
In the 1960s, extracts of pau d'arco demonstrated marked antitumorous effects in animals,
which drew the interest of the National Cancer Institute (NCI). Researchers decided that the
most potent single chemical for this activity was a naphthoquinone chemical named lapachol
and they concentrated solely on this single chemical in their subsequent cancer research. In a
1968 study, lapachol demonstrated highly significant activity against cancerous tumors in
rats. By 1970, NCI-backed research already was testing lapachol in human cancer patients.
The institute reported, however, that their first Phase I study failed to produce a therapeutic
effect without side effects—and they discontinued further cancer research shortly thereafter.
These side effects were nausea and vomiting and anti-vitamin K activity. Interestingly, other
chemicals in the whole plant extract (which, initially, showed positive antitumor effects at very
low toxicity) demonstrated positive effects on vitamin K and, conceivably, compensated for
lapachol's negative effect. Once again, instead of pursuing research on a complex
combination of at least 20 active chemicals in a whole plant extract (several of which had anti-tumor effects and other positive biological activities), research focused on a single, patentable
chemical—and it didn't work as well. Despite NCI's abandonment of the research, another
group developed a lapachol analog (which was patentable) in 1975. One study reported that
this lapachol analog increased the life span of mice inoculated with leukemic cells by over
80%. In a small, uncontrolled, 1980 study of nine human patients with various cancers (liver,
kidney, breast, prostate, and cervix), pure lapachol was reported to shrink tumors and reduce
pain caused by them—and three of the patients realized complete remissions.
Another chemical in pau d'arco, beta-lapachone, has been studied closely of late and a number of recent patents have been filed on it. It has demonstrated in laboratory studies to have activities similar to lapachol (antimicrobial, antifungal, antiviral, antitumorous, antileukemic, and anti-inflammatory), with few side effects. Research published from 2003 to 2005 provides important new insights into the possible molecular mechanisms of the anti-cancer activity of beta-lapachone specifically against prostate, colon, pancreatic, and lung cancers. In a 2002 U.S. patent, beta-lapachone was cited to have significant anticancerous activity against human cancer cell lines including: melanoma, promyelocytic leukemia, prostate, malignant glioma, colon, hepatoma, breast, ovarian, pancreatic, multiple myeloma cell lines and drug-resistant cell lines. In yet another U.S. patent, beta-lapachone was cited with the in vivo ability to inhibit the growth of prostate tumors.
Panda, S., et al. "Stem extract of Tabebuia chrysantha induces apoptosis by targeting sEGFR in Ehrlich ascites carcinoma." J. Ethnopharmacol. 2019 Feb; 235: 219-226.
Dias, R., et al. "β-Lapachone and its iodine derivatives cause cell cycle arrest at G(2)/M phase and reactive oxygen species-mediated apoptosis in human oral squamous cell carcinoma cells." Free Radic. Biol. Med. 2018 Oct; 126: 87-100.
Shankar, B., et al. "Lapachol inhibits glycolysis in cancer cells by targeting pyruvate kinase M2." PLoS One. 2018 Feb; 13(2): e0191419.
Hussain, H., and Green, I. "Lapachol and lapachone analogs: a journey of two decades of patent research (1997-2016)." Expert Opin. Ther. Pat. 2017 Oct; 27(10): 1111-1121.
Kee, J., et al. "β-lapachone inhibits lung metastasis of colorectal cancer by inducing apoptosis of CT26 cells." Integr. Cancer Ther. 2017 Dec; 16(4): 585-596.
Kee, J., et al. "β-Lapachone suppresses the lung metastasis of melanoma via the MAPK signaling pathway." PLoS One. 2017 May; 12(5): e0176937.
Beg, M., et al. "Using a novel NQO1 bioactivatable drug, beta-lapachone (ARQ761), to enhance chemotherapeutic effects by metabolic modulation in pancreatic cancer." J. Surg. Oncol. 2017 Jul; 116(1): 83-88.
Bang, W., et al. "β-lapachone suppresses the proliferation of human malignant melanoma cells by targeting specificity protein 1." Oncol Rep. 2016 Feb; 35(2): 1109-16.
Xu, H., et al. "Inhibitory effects of lapachol on rat C6 glioma in vitro and in vivo by targeting DNA topoisomerase I and topoisomerase II." J. Exp. Clin. Cancer Res. 2016 Nov; 35(1): 178.
Pires, T., et al. "Bioactive properties of Tabebuia impetiginosa-based phytopreparations and Phytoformulations: a comparison between extracts and dietary supplements." Molecules. 2015 Dec; 20(12): 22863-71.
Jeon, Y., et al. "Downregulation of Sp1 is involved in β-lapachone-induced cell cycle arrest and apoptosis in oral squamous cell carcinoma." Int. J. Oncol. 2015; 46(6): 2606-12.
Kung, H., etal. "Sulindac compounds facilitate the cytotoxicity of β-lapachone by up-regulation of NAD(P)H quinone oxidoreductase in human lung cancer cells." PLoS One. 2014 Feb; 9(2): e88122.
Sunassee, S., et al. "Cytotoxicity of lapachol, β-lapachone and related synthetic 1,4-naphthoquinones against oesophageal cancer cells." Eur. J. Med. Chem. 2013 Apr; 62: 98-110.
Oliveira Silva, E., et al. "Cytotoxicity of lapachol metabolites produced by probiotics." Lett. Appl. Microbiol. 2014 Jul; 59(1): 108-14.
Lamberti, M., et al. "Synergistic enhancement of antitumor effect of β-Lapachone by photodynamic induction of quinone oxidoreductase (NQO1)." Phytomedicine. 2013 Aug; 20(11): 1007-12.
Inagaki, R., et al. "Synthesis and cytotoxicity on human leukemia cells of furonaphthoquinones isolated from Tabebuia plants." Chem. Pharm. Bull. 2013; 61(6): 670-3.
Costa, W., et al. "Lapachol as an epithelial tumor inhibitor agent in Drosophila melanogaster heterozygote for tumor suppressor gene wts." Genet. Mol. Res. 2011 Dec; 10(4): 3236-45.
Sichaem, J., et al. "Tabebuialdehydes A-C, cyclopentene dialdehyde derivatives from the roots of Tabebuia rosea." Fitoterapia. 2012 Dec; 83(8): 1456-9.
Garkavtsev, I., et al. "Dehydro-alpha-lapachone, a plant product with antivascular activity." Proc. Natl. Acad. Sci. USA. 2011 Jul; 108(28): 11596-601.
Higa, R., et al. "Study of the antineoplastic action of Tabebuia avellanedae in carcinogenesis induced by azoxymethane in mice." Acta Cir. Bras. 2011 Apr; 26(2): 125-8.
Moon, D., et al. "Beta-lapachone (LAPA) decreases cell viability and telomerase activity in leukemia cells: suppression of telomerase activity by LAPA." J. Med. Food. 2010 Jun; 13(3): 481-8.
Mukherjee, B., et al. "Growth inhibition of estrogen receptor positive human breast cancer cells by Taheebo from the inner bark of Tabebuia avellandae tree." Int. J. Mol. Med. 2009 Aug; 24(2): 253-60.
Yamashita, M., et al. "Synthesis and evaluation of bioactive naphthoquinones from the Brazilian medicinal plant, Tabebuia avellanedae." Bioorg. Med. Chem. 2009 Sep; 17(17): 6286-91.
de Sousa, N., et al. "Modulatory effects of Tabebuia impetiginosa (Lamiales, Bignoniaceae) on doxorubicin-induced somatic mutation and recombination in Drosophila melanogaster" Genet. Mol. Biol. 2009 Apr-Jun; 32(2): 382–388.
Queiroz, M., et al. "Comparative studies of the effects of Tabebuia avellanedae bark extract and beta-lapachone on the hematopoietic response of tumour-bearing mice." J. Ethnopharmacol. 2008 May; 117(2): 228-35.
Kim, S., et al. "Induction of Egr-1 is associated with anti-metastatic and anti-invasive ability of beta-lapachone in human hepatocarcinoma cells." Biosci. Biotechnol. Biochem. 2007 Sep; 71(9): 2169-76.
Larsson, D., et al. "Identification and evaluation of potential anti-cancer drugs on human neuroendocrine tumor cell lines." Anticancer Res. 2006 Nov-Dec; 26(6B): 4125-9.
Bey, E., et al. "Mornings with Art, lessons learned: feedback regulation, restriction threshold biology, and redundancy govern molecular stress responses." J. Cell Physiol. 2006 Dec; 209(3): 604-10.
Kung, H., et al. "Involvement of NO/cGMP signaling in the apoptotic and anti-angiogenic effects of beta-lapachone on endothelial cells in vitro." J. Cell Physiol. 2006 Dec 27;
Bentle, M., et al. "Calcium-dependent modulation of poly(ADP-ribose) polymerase-1 alters cellular metabolism and DNA repair." J. Biol. Chem. 2006 Nov; 281(44): 33684-96.
Sun, X., et al. "Selective induction of necrotic cell death in cancer cells by beta-lapachone through activation of DNA damage response pathway." Cell Cycle. 2006 Sep; 5(17): 2029-35.
Woo, H., et al. "Beta-lapachone, a quinone isolated from Tabebuia avellanedae, induces apoptosis in HepG2 hepatoma cell line through induction of Bax and activation of caspase." J. Med. Food. 2006 Summer; 9(2): 161-8.
Suzuki, M., et al. "Synergistic effects of radiation and beta-lapachone in DU-145 human prostate cancer cells in vitro." Radiat. Res. 2006; 165(5): 525-31.
Lee, J., et al. "Beta-lapachone induces growth inhibition and apoptosis in bladder cancer cells by modulation of Bcl-2 family and activation of caspases." Exp. Oncol. 2006 Mar; 28(1): 30-5.
Lee, J., et al. "Down-regulation of cyclooxygenase-2 and telomerase activity by beta-lapachone in human prostate carcinoma cells." Pharmacol. Res. 2005; 51(6): 553-60.
Reinicke, K., et al. "Development of beta-lapachone prodrugs for therapy against human cancer cells with elevated NAD(P)H:quinone oxidoreductase 1 levels." Clin. Cancer Res. 2005 Apr; 11(8): 3055-64.
Woo, H., et al. "Growth inhibition of A549 human lung carcinoma cells by beta-lapachone through induction of apoptosis and inhibition of telomerase activity." Int. J. Oncol. 2005; 26(4): 1017-23.
Park, H., et al. "Heat-induced up-regulation of NAD(P)H:quinone oxidoreductase potentiates anticancer effects of beta-lapachone." Clin. Cancer Res. 2005 Dec; 11(24 Pt 1): 8866-71.
Balassiano, I., et al. "Demonstration of the lapachol as a potential drug for reducing cancer metastasis. Oncol. Rep. 2005; 13(2): 329-33.
Ough, M., et al. "Efficacy of beta-lapachone in pancreatic cancer treatment: exploiting the novel, therapeutic target NQO1." Cancer Biol. Ther. 2005 Jan; 4(1): 95-102.
Park, H., et al. "Susceptibility of cancer cells to beta-lapachone is enhanced by ionizing radiation." Int. J. Radiat. Oncol. Biol. Phys. 2005 Jan; 61(1): 212-9.
Kumi-Diaka, J., et al. "Potential mechanism of phytochemical-induced apoptosis in human prostate adenocarcinoma cells: Therapeutic synergy in genistein and beta-lapachone combination treatment." Cancer Cell Int. 2004 Aug; 4(1): 5.
Choi, B., et al. "Beta-Lapachone-induced apoptosis is associated with activation of caspase-3 and inactivation of NF-kappaB in human colon cancer HCT-116 cells." Anticancer Drugs. 2003 Nov; 14(10): 845-50.
Renou, S., et al. "Monoarylhydrazones of alpha-lapachone: synthesis, chemical properties and antineoplastic activity." Pharmazie. 2003 Oct; 58(10): 690-5.
Choi, Y. H., et al. "Suppression of human prostate cancer cell growth by beta-Lapachone via down-regulation of PRB phosphorylation and induction of Cdk Inhibitor p21(WAF1/CIP1)." J. Biochem. Mol. Biol. 2003 Mar; 36(2): 223-9.
Pardee, A., et al, "Cancer therapy with beta-lapachone." Curr. Cancer Drug Targets. 2002 Sep; 2(3): 227-42.
Colman de Saizarbitoria, T., et al. "Bioactive furonaphtoquinones from Tabebuia barbata (Bignoniaceae)." Acta Cient. Venez. 1997; 48(1): 42-6.
Ueda, S., et al. "Production of anti-tumour-promoting furanonaphthoquinones in Tabebuia avellanedae cell cultures." Phytochemistry. 1994 May; 36(2): 323-5.
Schuerch, A., et al. "B-Lapachone, an inhibitor of oncornavirus reverse transcriptase and eukarotic DBA Polymerase-A. Inhibitory effect, thiol dependency and specificity." Eur. J. Biochem. 1978; 84: 197-205.
Linardi, M., et al. "A lapachol derivative active against mouse lymphocyte leukemia P-388." J. Med. Chem. 1975; 18(11): 1159-62.
Block, J., et al. "Early clinical studies with lapachol (NSC-11905)." Cancer Chemother. Rep. 1974; 4: 27-8.
Santana, C., et al. "Preliminary observation with the use of lapachol in human patients bearing malignant neoplasms." Revista do Instituto de Antibioticos 1971; 20: 61-8.
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Mullaca (Physalis angulata)
Mullaca, and its novel plant steroids, have shown strong in vitro and in vivo (mice) cytotoxic activity against numerous types of cancer including leukemia, lung, colon, cervix and melanoma cancer cells.* It has also evidenced significant immunostimulant actions.*
Boonsombat, J., et al. "A new 22,26-seco physalin steroid from Physalis angulata." Nat. Prod. Res. 2019 Jan 8: 1-8.
Zhang, Y., et al. "Target discovery of cytotoxic withanolides from Physalis angulata var. villosa via reactivity-based screening." J. Pharm. Biomed. Anal. 2018 Mar; 151: 194-199.
Gao, C., et al. "Cytotoxic withanolides from Physalis angulata." Nat. Prod. Res. 2018 Mar; 32(6): 676-681.
Ma, T., et al. "Downregulation of TIGAR sensitizes the antitumor effect of physapubenolide through increasing intracellular ROS levels to trigger apoptosis and autophagosome formation in human breast carcinoma cells." Biochem. Pharmacol. 2017 Nov; 143: 90-106.
Sun, C., et al. "Physalins V-IX, 16,24-cyclo-13,14-seco withanolides from Physalis angulata and their antiproliferative and anti-inflammatory activities. Sci. Rep. 2017 Jun; 7(1): 4057.
Sun, C., et al. "Antiproliferative and anti-inflammatory withanolides from Physalis angulata." J. Nat. Prod. 2016 Jun; 79(6): 1586-97.
Gao. C., et al. "Three new cytotoxic withanolides from the chinese folk medicine Physalis angulata." Nat. Prod. Commun. 2015 Dec; 10(12): 2059-62.
Maldonado, E., et al. "Cytotoxic 20,24-epoxywithanolides from Physalis angulata." Steroids. 2015 Dec; 104: 72-8.
Men, R.,et al. "Unprecedent aminophysalin from Physalis angulata." Steroids. 2014 Oct; 88:60-5.
Ding, H., et al. "Induction of quinone reductase (QR) by withanolides isolated from Physalis angulata L. var. villosa Bonati (Solanaceae). Steroids. 2014 Aug; 86: 32-8.
Mangwala, P., et al. "Isolation, pharmacological activity and structure determination of physalin B and 5β,6β-epoxyphysalin B isolated from Congolese Physalis angulata L.". Acta Crystallogr. C. 2013 Dec; 69(Pt 12): 1557-62.
Reyes-Reyes, E., et al. "Physangulidine A, a withanolide from Physalis angulata, perturbs the cell cycle and induces cell death by apoptosis in prostate cancer cells." J. Nat. Prod. 2013 Jan; 76(1): 2-7.
Wu, S., et al. "Physalin F induces cell apoptosis in human renal carcinoma cells by targeting NF-kappaB and generating reactive oxygen species." PLoS One. 2012; 7(7): e40727.
Jin, Z., et al. "Physangulidines A, B, and C: three new antiproliferative withanolides from Physalis angulata L." Org. Lett. 2012 Mar 2; 14(5): 1230-3.
Hsu, C., et al. "Physalin B from Physalis angulata triggers the NOXA-related apoptosis pathway of human melanoma A375 cells." Food Chem Toxicol. 2012 Mar; 50(3-4): 619-24.
Hseu, Y., et al. "Inhibitory effects of Physalis angulata on tumor metastasis and angiogenesis." J. Ethnopharmacol. 2011 Jun; 135(3): 762-71.
Lee, H., et al. "Oxidative stress involvement in Physalis angulata-induced apoptosis in human oral cancer cells." Food Chem. Toxicol. 2009 Mar;47(3):561-70.
Lee, S., et al. "Withangulatin I, a new cytotoxic withanolide from Physalis angulata." Chem. Pharm. Bull (Tokyo). 2008 Feb; 56(2): 234-6.
Damu, A., et al. "Isolation, structures, and structure - cytotoxic activity relationships of withanolides and physalins from Physalis angulata." J. Nat. Prod. 2007 Jul;70(7):1146-52.
He, Q., et al. "Cytotoxic withanolides from Physalis angulata L." Chem. Biodivers. 2007 Mar; 4(3): 443-9.
Ausseil, F., et al. "High-throughput bioluminescence screening of ubiquitin-proteasome pathway inhibitors from chemical and natural sources." J. Biomol. Screen. 2007 Feb; 12(1): 106-16.
Kuo, P., et al. "Physanolide A, a novel skeleton steroid, and other cytotoxic principles from Physalis angulata." Org. Lett. 2006 Jul; 8(14): 2953-6.
Ichikawa, H., et al. "Withanolides potentiate apoptosis, inhibit invasion, and abolish osteoclastogenesis through suppression of nuclear factor-kappaB (NF-kappaB) activation and NF-kappaB-regulated gene expression." Mol. Cancer Ther. 2006; 5(6): 1434-45.
Magalhaes, H. I., et al. "In-vitro and in-vivo antitumour activity of physalins B and D from Physalis angulata." J. Pharm. Pharmacol. 2006; 58(2): 235-41.
Jacobo-Herrera, N., et al. "Physalins from Witheringia solanacea as modulators of the NF-kappaB cascade." J. Nat. Prod. 2006; 69(3): 328-31.
Magalhaes, H., et al. "In-vitro and in-vivo antitumour activity of physalins B and D from Physalis angulata." J. Pharm. Pharmacol. 2006 Feb; 58(2): 235-41.
Hsieh, W., et al. "Physalis angulata induced G2/M phase arrest in human breast cancer cells." Food Chem Toxicol. 2006; 44(7): 974-83.
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Wu, S., et al. "Antihepatoma activity of Physalis angulata and P. peruviana extracts and their effects on apoptosis in human Hep G2 cells." Life Sci. 2004 Mar; 74(16): 2061-73.
Leyon, P., et al. "Effect of Withania somnifera on B16F-10 melanoma induced metastasis in mice." Phytother. Res. 2004; 18(2): 118-22.
Kawai, M., et al. "Cytotoxic activity of physalins and related compounds against HeLa cells." Pharmazie 2002; 57(5): 348-50.
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Vassourinha (Scoparia dulcis)
Many of vassourinha's active biological properties, including its anticancerous properties, are
attributed to various flavone and terpene chemicals, some only found in vassourinha.. The
main chemicals being studied for their actions against cancer are scopadulcic acids A and B,
scopadiol, scopadulciol, scopadulin, scoparic acids A, B, and C, and betulinic acid.
Wang, W., et al. "Betulinic acid induces apoptosis and suppresses metastasis in hepatocellular carcinoma cell lines in vitro and in vivo." J. Cell. Mol. Med. 2019 Jan; 23(1): 586-595
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Sousa, J., et al. "Recent developments in the functionalization of betulinic acid and its natural analogues: a route to new bioactive compounds." Molecules. 2019 Jan; 24(2).
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Yang, C., et al. "Betulinic acid induces apoptosis and inhibits metastasis of human renal carcinoma cells in vitro and in vivo." J. Cell. Biochem. 2018 Nov; 119(10): 8611-8622.
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Wu, W., et al. "Benzoxazinoids from Scoparia dulcis (sweet broomweed) with antiproliferative activity against the DU-145 human prostate cancer cell line." Phytochemistry. 2012 Nov; 83: 110-5.
Hayashi, T., et al. "Investigation on traditional medicines of Guarany Indio and studies on diterpenes from Scoparia dulcis." Yakugaku Zasshi. 2011; 131(9): 1259-69.
Kessler, J., et al. "Broad in vitro efficacy of plant-derived betulinic acid against cell lines derived from the most prevalent human cancer types." Cancer Lett. 2007 Jun; 251(1): 132-45.
Mukherjee, R., et al. "Betulinic acid derivatives as anticancer agents: structure activity relationship." Anticancer Agents Med. Chem. 2006 May; 6(3): 271-9.
Phan, M., et al. "Chemical and biological evaluation on scopadulane-type diterpenoids from Scoparia dulcis of Vietnamese origin." Chem. Pharm. Bull. 2006 Apr; 54(4): 546-9.
Hayashi, K., et al. "The role of a HSV thymidine kinase stimulating substance, scopadulciol, in improving the efficacy of cancer gene therapy." J. Gene Med. 2006 Aug; 8(8): 1056-67.
Kasperczyk, H., et al. "Betulinic acid as new activator of NF-kappaB: molecular mechanisms and implications for cancer therapy." Oncogene. 2005 Oct; 24(46): 6945-56.
Fulda, S., et al. "Sensitization for anticancer drug-induced apoptosis by betulinic acid." Neoplasia. 2005; 7(2): 162-70.
Garg, A., et al. "Chemosensitization and radiosensitization of tumors by plant polyphenols." Antioxid. Redox. Signal. 2005; 7(11-12): 1630-47.
Wada, S., et al. "Betulinic acid and its derivatives, potent DNA topoisomerase II inhibitors, from the bark of Bischofia javanica." Chem. Biodivers. 2005 May; 2(5): 689-94.
Hayashi, K., et al. "Evaluation of scopadulciol-related molecules for their stimulatory effect on the cytotoxicity of acyclovir and ganciclovir against Herpes simplex virus type 1 thymidine kinase gene-transfected HeLa cells." Chem. Pharm. Bull. 2004; 52(8):1015-7.
Ahsan, M., et al. "Cytotoxic diterpenes from Scoparia dulcis." J. Nat. Prod. 2003; 66(7): 958-61.
Fulda, S., et al. "Betulinic acid induces apoptosis through a direct effect on mitochondria in neuroecto-dermal tumors." Med. Pediatr. Oncol. 2000; 35(6): 616-18.
Fulda, S., et al. "Betulinic acid: A new cytotoxic agent against malignant brain-tumor cells." Int. J. Cancer 1999; 82(3): 435-41.
Noda, Y., et al. "Enhanced cytotoxicity of some triterpenes toward leukemia L1210 cells cultured in low pH media; possibility of a new mode of cell killing." Chem. Pharm. Bull. 1997; 45(10): 1665-70.
Arisawa, M. "Cell growth inhibition of KB cells by plant extracts." Natural Med. 1994; 48(4): 338-47.
Nishino, H. "Antitumor-promoting activity of scopadulcic acid B, isolated from the medicinal plant Scoparia dulcis L." Oncology. 1993; 50(2): 100-3.
Hayashi, T., et al. "Scoparic acid A, a beta-glucuronidase inhibitor from Scoparia dulcis." J. Nat. Prod. 1992; 55(12): 1748
Hayashi, R., et al. "A cytotoxic flavone from Scoparia dulcis L." Chem. Pharm. Bull. 1988; 36: 4849-51.
Mutamba (Guazuma ulmifolia)
Thus far, mutamba has been documented to contain at least 4 different plant chemicals that have actions against cancer. Several of these chemicals are being synthesized in an attempt to create patentable derivatives as new cancer drugs.
Kumar, R., et al. "Procyanidin B2 3,3″-di-O-gallate induces oxidative stress-mediated cell death in prostate cancer cells via inhibiting MAP kinase phosphatase activity and activating ERK1/2 and AMPK." Mol. Carcinog. 2018 Jan; 57(1): 57-69.
Karthika, V., et al. "Guazuma ulmifolia bark-synthesized Ag, Au and Ag/Au alloy nanoparticles: Photocatalytic potential, DNA/protein interactions, anticancer activity and toxicity against 14 species of microbial pathogens. J. Photochem. Photobiol B. 2017 Feb; 167: 189-199.
Da'i, M., et al. "Antiproliferative properties of tiliroside from Guazuma ulmifolia lamk (leaves) on T47D and MCF7 cancer cell lines." Natl. J Physiol. Pharm. Pharmacol.. 2016; 6(6): 627-633.
Calixto Júnior, J., et al. "Phenolic composition and antiparasitic activity of plants from the Brazilian Northeast "Cerrado"" Saudi. J. Biol Sci. 2016 May; 23(3): 434-40.
Shilpi, A., et al. "Mechanisms of DNA methyltransferase-inhibitor interactions: Procyanidin B2 shows new promise for therapeutic intervention of cancer." Chem. Biol. Interact. 2015 May; 233: 122-38.
Shay, J., et al. "Molecular mechanisms and therapeutic effects of (-)-epicatechin and other polyphenols in cancer, inflammation, diabetes, and neurodegeneration." Oxid. Med. Cell Longev. 2015; 2015: 181260
Maldini, M., et al. "Flavanocoumarins from Guazuma ulmifolia bark and evaluation of their affinity for STAT1." Phytochemistry. 2013 Feb; 86: 64-71.
Avelar, M., et al. "Procyanidin B2 cytotoxicity to MCF-7 human breast adenocarcinoma cells." Indian J. Pharm Sci. 2012 Jul; 74(4): 351-5.
Jacobo-Salcedo Mdel, R., et al. "Antimicrobial and cytotoxic effects of Mexican medicinal plants." Nat Prod Commun. 2011 Dec; 6(12): 1925-8.
Cuca, L, et al. "Cytotoxic effect of some natural compounds isolated from Lauraceae plants and synthetic derivatives." Biomedica. 2011 Jul-Sep; 31(3): 335-43.
Hueso-Falcón, I., et al. "Synthesis and induction of apoptosis signaling pathway of ent-kaurane derivatives." Bioorg. Med. Chem. 2010 Feb 15;18(4):1724-35.
Cavalcanti, B., et al. "Kauren-19-oic acid induces DNA damage followed by apoptosis in human leukemia cells." J. Appl. Toxicol. 2009 Oct; 29(7): 560-8.
Seigler, D. S. "Cyanogenic glycosides and menisdaurin from Guazuma ulmifolia, Ostrya virgininana, Tiquilia plicata and Tiquilia canescens." Phytochemistry. 2005 Jul; 66(13): 1567-80.
Ito, H., et al. "Antitumor activity of compounds isolated from leaves of Eriobotrya japonica." J. Agric. Food Chem. 2002; 50(8): 2400-3.
Kashiwada, Y., et al. "Antitumor agents, 129. Tannins and related compounds as selective cytotoxic agents." J. Nat. Prod. 1992; 55(8): 1033-43.
Nascimento, S. C., et al. "Antimicrobial and cytotoxic activities in plants from Pernambuco, Brazil." Fitoterapia. 1990; 61(4): 353-55.