n-tense topical annona muricata N-Tense Topical

2 Fluid Ounces (60 ml)

This product is no longer sold by Raintree Nutrition, Inc. See the main product page for more information why. Try doing a google search or see the rainforest products page to find other companies selling rainforest herbal supplements or rainforest plants if you want to make this rainforest formula yourself.

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.

Contraindications: None reported

Drug Interactions: None known.

Other Observations: This extract will stain clothing and other textiles.

Third-Party Published Research*

This actual rainforest formula has not been the subject of any clinical research. A partial listing of third-party published research on each herbal ingredient in the formula is shown below. Please refer to the plant database files by clicking on the plant names below to see all available documentation and research on each plant ingredient.

Sangre de Grado (Croton lechleri)
Sangre de grado has demonstrated anticancerous actions in the following research studies.* One recent study indicated that it inhibited the growth of melanoma skin cancer.*
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.
Alonso-Castro, A., et al. "Antitumor effect of Croton lechleri Mull. Arg. (Euphorbiaceae). J Ethnopharmacol. 2012 Mar 27;140(2):438-42.
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. P., 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.*
dos Santos Júnior, 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 80 Annonaceous acetogenins which have shown in laboratory studies to be selectively cytotoxic to cancer cells without toxicity to healthy cells.* Over 30 published studies report that these acetogenins have demonstrated selective cytotoxicity to tumor cells with as little as 1 part per million.*
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 1;323(1):29-40.
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. 2012 Nov 21. [Epub ahead of print]
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. 2012 Nov 21. [Epub ahead of print]
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.
Chen, Y., et al. "Anti-tumor activity of Annona squamosa seeds extract containing annonaceous acetogenin compounds." J Ethnopharmacol. 2012 Jul 13;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 15;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 24;15(12):8534-42.
Ko, Y., et al. "Annonacin induces cell cycle-dependent growth arrest and apoptosis in estrogen receptor-beta-related pathways in MCF-7 cells." J Ethnopharmacol. 2011 Oct 11;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 15;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 28;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 15;19(8):2199-202.
Kojima, N. “Systematic synthesis of antitumor Annonaceous acetogenins” Yakugaku Zasshi. 2004; 124(10): 673-81
Tormo, J. R., 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. 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. 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. R., et al. “Novel cytotoxic Annonaceous acetogenins from Annona muricata.J. Nat. Prod. 2001; 64(7): 925-31.
Jaramillo, M. C., 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. S., et al. “Muricoreacin and murihexocin C, mono-tetrahydrofuran acetogenins, from the leaves of Annona muricata.Phytochemistry. 1998; 49(2): 565-71.
Kim, G. S., 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. E., 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. H., 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. E., 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. E., 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. E., 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.*
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 a group of chemicals called maytansinoids which have showed potent antitumorous and anticancerous activities at very low dosages.* Other compounds in the plant including one name pristimerin have shown in research to possess cytotoxic and/or inhibitory activity against various leukemia and cancer tumor cells.*
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 5;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 23;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.
Monache, F. D., et al., “Maitenin: A new antitumoral substance from Maytenus sp.” Gazetta Chimica Italiana 1972; 102: 317–20.
de Santana, C. F., et al. “Primeiras observacoes sobre o emprego da maitenina em pacientes cancerosos.” Rev. Inst. Antibiot. 1971; 11: 37–49.
Hartwell, J. L. “Plants used against cancer: A survey.” Lloydia. 1968; 31: 114.

Pau d'arco (Tabebuia impetiginosa)
Pau d'arco contains two chemicals called lapachol and beta-lapachone which have widely been documented with strong anticancerous and antitumorous actions in many studies over the last 30 years.*
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 22;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 U S A. 2011 Jul 12;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 1;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 8;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. E., 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. A., 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. N., 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. S., 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. J., 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. I., 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. H., 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. E., 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. J., 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. J., 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. T., 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. J., 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. T., 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. G., 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.
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. R., 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. D. C., et al. “A lapachol derivative active against mouse lymphocyte leukemia P-388.” J. Med. Chem. 1975; 18(11): 1159–62.
Block, J. B., et al. “Early clinical studies with lapachol (NSC-11905).” Cancer Chemother. Rep. 1974; 4: 27–8.
Santana, C. F., et al. “Preliminary observation with the use of lapachol in human patients bearing malignant neoplasms.” Revista do Instituto de Antibioticos 1971; 20: 61–8.
Rao, K. V., et al. “Recognition and evaluation of lapachol as an antitumor agent.” Canc. Res. 1968; 28: 1952–54.

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.*
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 1;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. 2006 Dec 14;
Kuo, P. C., 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. J., et al. "Physalins from Witheringia solanacea as modulators of the NF-kappaB cascade." J. Nat. Prod. 2006; 69(3): 328-31.
Magalhaes, H. I., 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. T., et al. “Physalis angulata induced G2/M phase arrest in human breast cancer cells.” Food Chem Toxicol. 2006; 44(7): 974-83.
Lee, C. C., et al. "Cytotoxicity of plants from Malaysia and Thailand used traditionally to treat cancer." J. Ethnopharmacol. 2005 Sep; 100(3): 237-43.
Wu, S. J., 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. V., 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.
Ismail, N., et al. “A novel cytotoxic flavonoid glycoside from Physalis angulata.” Fitoterapia. 2001 Aug. 72(6):676–79.
Lee, Y. C., et al. “Integrity of intermediate filaments is associated with the development of acquired thermotolerance in 9L rat brain tumor cells.” J. Cell. Biochem. 1995; 57(1): 150–62.
Perng, M. D., et al. “Induction of aggregation and augmentation of protein kinase-mediated phosphorylation of purified vimentin intermediate filaments by withangulatin A.” Mol. Pharmacol. 1994; 46(4): 612–17.
Chiang, H., et al. “Antitumor agent, physalin F from Physalis angulata L.” Anticancer Res. 1992; 12(3): 837–43.
Chiang, H., et al. “Inhibitory effects of physalin B and physalin F on various human leukemia cells in vitro.” Anticancer Res. 1992; 12(4): 1155–62.
Kusumoto, I., et al. “Inhibitory effect of Indonesian plant extracts on reverse transcriptase of an RNA tumour virus (I).” Phytother. Res. 1992; 6(5): 241–44.
Lee, W. C., et al. “Induction of heat-shock response and alterations of protein phosphorylation by a novel topoisomerase II inhibitor, withangulatin A, in 9L rat brain tumor cells.” Cell Physiol. 1991; 149(1): 66-67.
Chen, C. M., et al. “Withangulatin A, a new withanolide from Physalis angulata.” Heterocycles. 1990; 31(7):1371–75.
Basey, K., et al. “Phygrine, an alkaloid from Physalis species.” Phytochemistry. 1992; 31(12): 4173–76.
Juang, J. K., et al. “A new compound, withangulatin A, promotes type II DNA topoisomerasemediated DNA damage.” Biochem. Biophys. Res. Commun. 1989; 159(3): 1128–34.
Anon. “Biological assay of antitumor agents from natural products.” Abstr.: Seminar on the Development of Drugs from Medicinal Plants Organized by the Department of Medical Science Department at Thai Farmer Bank, Bangkok, Thailand 1982; 129.
Antoun, M. D., et al. “Potential antitumor agents. XVII. physalin B and 25,26-epidihydrophysalin C from Witheringia coccoloboides.” J. Nat. Prod. 1981; 44(5): 579–85.

Vassourinha (Scoparia dulcis)
A crude extract of vassourinha was reported to be active against human oral epidermoid carcinoma cells (66% inhibition) in vitro.* Crude extracts from the plant demonstrated cytotoxicity towards six human stomach cancer cell lines.* These antitumor actions were linked to two phytochemicals, scopadulcic acid B and betulinic acid. These two chemicals have been documented with anticarcinomic, antimelanomic, cytotoxic, and antiviral properties in other research studies.*
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. H., et al. "Broad in vitro efficacy of plant-derived betulinic acid against cell lines derived from the most prevalent human cancer types." Cancer Lett. 2006 Dec 12;
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. G., 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. K., 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. J., et al. “A cytotoxic flavone from Scoparia dulcis L.” Chem. Pharm. Bull. 1988; 36: 4849–51.

Mutamba (Guazuma ulmifolia)
Mutamba, in one in vitro study, exhibited strong activity against human oral epidermoid carcinoma cells by inhibiting growth by 97.3%.* Mutamba also contains procyanidin B-2 which has shown in other in vitro studies to have antitumor activity.* In one study it showed activity towards melanoma cells with an ED50 of 1-4 mcg/ml.* Some of the latest research on mutamba has focused on the antioxidants in the plant and their ability to interfere with prostaglandin synthetase.*
Maldini, M., et al. "Flavanocoumarins from Guazuma ulmifolia bark and evaluation of their affinity for STAT1." Phytochemistry. 2012 Nov 14. doi:pii: S0031-9422(12)00467-0. 10.1016/j.phytochem.2012.10.011. [Epub ahead of print]
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.

*The statements contained herein have not been evaluated
by the Food and Drug Administration. The information contained herein is intended and provided for education, research, entertainment and information purposes only. This information is not intended to be used to diagnose, prescribe or replace proper medical care. The plants and/or formulas described herein are not intended to treat, cure, diagnose, mitigate or prevent any disease and no medical claims are made.
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Last updated 12-30-2012