Better than Graviola alone!
120 capsules (700 mg each)
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 combines the rainforest's most potent and powerful plants into one synergistic formula. These power plants of the rainforest have been independently documented around the world with biological actions against cancer (see published independent reseach below).* This unique formula contains 50% graviola combined with 7 other plants that have similar properties and actions as graviola. Most find this unique blend of rainforest plants to have synergistic actions and provide better results than graviola alone.
This product was featured in three articles by the Health Sciences Institute:
First Article page 1 on graviola, page 4 on N-Tense,
Second Article page 6.
Third Article page 3.
For more information on the individual ingredients in N-Tense, follow the links provided below to the plant database files in the Tropical Plant Database. More information can also be found in the new Anti-Cancerous Guide. Don't forget to check out the new Discussion Forums to see if anyone is talking about how they are using this natural rainforest remedy or to share your own experience with it.
Ingredients: A synergistic blend of graviola, mullaca, guacatonga, espinheira santa, bitter melon, vassourinha, mutamba, and cat’s claw. To prepare this natural remedy yourself: use 10 parts graviola, 2 parts mullaca, 2 parts guacatonga, 2 parts espinheira santa, and 1 part each of bitter melon, vassourinha, mutamba and cat's claw. To make a small amount... 1 part could be a tablespoon (you'd have 20 tablespoons of the blended herbal formula). For larger amounts use 1 part as one ounce or one cup or one pound. Combine all the herbs together well. The formula can then be stuffed into capsules or brewed into tea, stirred into juice or other liquid, or taken however you'd like.
Suggested Use: Take 2-3 grams by weight (or about 1 1/2 teaspoon by volume) three times daily, or as directed by a healthcare professional.
Drug Interactions: This product may enhance or increase the effect of high blood pressure drugs.
- Not to be used during pregnancy or while breast-feeding.
- Several ingredients in this formula have demonstrated hypotensive, vasodilator, and cardiodepressant activities in animal studies. People with low blood pressure should monitor their blood pressure for this possible effect.
Other Practitioner Observations:
- Several ingredients in this formula have demonstrated significant in vitro antimicrobial properties. Supplementing the diet with probiotics (like acidophilus found in live-cultured yogurt) is advisable when this product is used for longer than 30 days.
- Taking CoQ10 and other supplements which increase cellular ATP might reduce the effects of N-Tense.
Third-Party Published Research*
This actual herbal formula has not been the subject of any clinical research. A partial listing of
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.
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.
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.
Guacatonga (Casearia sylvestris)
Guacatonga contains a group of chemicals called clerodane diterpenes which are being researched and patented for their anti-cancerous actions.*
Prieto, A., et al. "Assessment of the chemopreventive effect of casearin B, a clerodane diterpene extracted from Casearia sylvestris (Salicaceae)." Food Chem Toxicol. 2012 Nov 28.
Ismail, M., et al. "Anticancer properties and phenolic contents of sequentially prepared extracts from different parts of selected medicinal plants indigenous to Malaysia." Molecules. 2012 May 14;17(5):5745-56.
Faiella, L., et al. "A chemical proteomics approach reveals Hsp27 as a target for proapoptotic clerodane diterpenes." Mol Biosyst. 2012 Oct;8(10):2637-44.
Ferreira, P., et al. "Folk uses and pharmacological properties of Casearia sylvestris: a medicinal review." An Acad Bras Cienc. 2011 Dec;83(4):1373-84.
Vieira-Júnior, G., et al. "Cytotoxic clerodane diterpenes from Casearia rupestris." J Nat Prod. 2011 Apr 25;74(4):776-81.
Ferreira, P., et al. "Casearin X exhibits cytotoxic effects in leukemia cells triggered by apoptosis." Chem Biol Interact. 2010 Dec 5;188(3):497-504.
dos Santos, A., et al. "Casearin X, its degradation product and other clerodane diterpenes from leaves of Casearia sylvestris: evaluation of cytotoxicity against normal and tumor human cells." Chem Biodivers. 2010 Jan;7(1):205-15.
Vieira, G., et al. "Cytotoxic clerodane diterpenoids from Casearia obliqua." J Nat Prod. 2009 Oct;72(10):1847-50.
de Oliveira, A., et al. "Ethanolic extract of Casearia sylvestris and its clerodane diterpen (caseargrewiin F) protect against DNA damage at low concentrations and cause DNA damage at high concentrations in mice's blood cells." Mutagenesis. 2009 Nov;24(6):501-6.
de Mesquita, M., et al. "Cytotoxic activity of Brazilian Cerrado plants used in traditional medicine against cancer cell lines." J Ethnopharmacol. 2009 Jun 25;123(3):439-45.
Da Silva, S., et al. "Chemotherapeutic potential of two gallic acid derivative compounds from leaves of Casearia sylvestris Sw (Flacourtiaceae)." Eur J Pharmacol. 2009 Apr 17;608(1-3):76-83.
Balunas, M. J., et al. "Relationships between inhibitory activity against a cancer cell line panel, profiles of plants collected, and compound classes isolated in an anticancer drug discovery project." Chem. Biodivers. 2006; 3(8): 897-915.
Shen, Y. C., et al. "Cytotoxic clerodane diterpenoids from Casearia membranacea." J. Nat. Prod. 2005; 68(11): 1665-8.
Maistro, E. L., et al. “Evaluation of the genotoxic potential of the Casearia sylvestris extract on HTC and V79 cells by the comet assay.” Toxicol. In Vitro. 2004 Jun; 18(3): 337-42.
Oberlies, N. H., et al. “Novel bioactive clerodane diterpenoids from the leaves and twigs of Casearia sylvestris.” J. Nat. Prod. 2002; 65(2): 95–99.
Sai Prakash, C. V., et al. “Structure and stereochemistry of new cytotoxic clerodane diterpenoids from the bark of Casearia lucida from the Madagascar rainforest.” J. Nat. Prod. 2002; 65(2): 100-7.
Beutler, J. A. “Novel cytotoxic diterpenes from Casearia arborea.” J. Nat. Prod. 2000; 63(5): 657-61.
Almeida, A. “Antitumor and anti-inflammatory effects of extract from Casearia sylvestris: comparative study with Piroxicam and Meloxicam.” Instituto de Ciencias Biomedicas, University of Sao Paulo (Dissertation, 4/02/99).
Itokawa, H., et al. “Antitumor substances from South American plants.” J. Pharmacobio. Dyn. 1992; 15(1): S-2-.
Morita, H., et al. “Structures and cytotoxic activity relationship of casearins, new clerodane diterpenes from Casearia sylvestris Sw.” Chem. Pharm. Bull. (Tokyo) 1991 Dec; 39(3): 693–97.
Itokawa, H., et al. “New antitumor principles, casearins A–F, for Casearia sylvestris Sw. (Flacourtiaceae).” Chem. Pharm. Bull. (Tokyo) 1990; 38(12): 3384–88.
Itokawa, H., et al. “Isolation of diterpenes as antitumor agents from plants.” Patent—Japan Kokai Tokyo Koho–01 1989; 149, 779: 6pp.
Itokawa, H., et al. “Antitumor principles from Casearia sylvestris Sw. (Flacourtiaceae), structure elucidation of new clerodane diterpenes by 2-D NMR spectroscopy.” Chem. Pharm. Bull. (Tokyo) 1988 March; 36(4): 1585–88.
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 named cangorins 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.
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Bitter Melon (Momordica charantia)
Bitter melon has been shown in studies over the last 10 years to have antitumorous and anticancerous properties.* The plant contains the phytochemicals 5-hydroxytryptamine, zeaxanthin, cryptoxanthin, and lanosterol—all of which are documented to be anticancerous, antimutagenic and/or cytoprotective.*
Li, C., et al. "Momordica charantia Extract Induces Apoptosis in Human Cancer Cells through Caspase- and Mitochondria-Dependent Pathways." Evid Based Complement Alternat Med. 2012;2012:261971.
Chipps, E., et al. "Cytotoxicity analysis of active components in bitter melon (Momordica charantia) seed extracts using human embryonic kidney and colon tumor cells." Nat Prod Commun. 2012 Sep;7(9):1203-8.
Tabata, K., et al. "Kuguaglycoside C, a constituent of Momordica charantia, induces caspase-independent cell death of neuroblastoma cells." Cancer Sci. 2012 Dec;103(12):2153-8.
Meng, Y., et al. "Preparation of an antitumor and antivirus agent: chemical modification of ?-MMC and MAP30 from Momordica Charantia L. with covalent conjugation of polyethyelene glycol." Int J Nanomedicine. 2012;7:3133-42.
Soundararajan, R., et al. "Antileukemic Potential of Momordica charantia Seed Extracts on Human Myeloid Leukemic HL60 Cells." Evid Based Complement Alternat Med. 2012;2012:732404.
Fang, E., et al. "The MAP30 protein from bitter gourd (Momordica charantia) seeds promotes apoptosis in liver cancer cells in vitro and in vivo." Cancer Lett. 2012 Nov 1;324(1):66-74.
Fang, E., et al. "In vitro and in vivo anticarcinogenic effects of RNase MC2, a ribonuclease isolated from dietary bitter gourd, toward human liver cancer cells." Int J Biochem Cell Biol. 2012 Aug;44(8):1351-60.
Wang, X., et al. "Structures of new triterpenoids and cytotoxicity activities of the isolated major compounds from the fruit of Momordica charantia L." J Agric Food Chem. 2012 Apr 18;60(15):3927-33.
Zhang, J., et al. "Cucurbitane triterpenoids from the leaves of Momordica charantia, and their cancer chemopreventive effects and cytotoxicities." Chem Biodivers. 2012 Feb;9(2):428-40.
Pitchakarn, P, et al. "Kuguacin J, a triterpeniod from Momordica charantia leaf, modulates the progression of androgen-independent human prostate cancer cell line, PC3." Food Chem Toxicol. 2012 Mar;50(3-4):840-7.
Brennan, V., et al. "Bitter melon (Momordica charantia) extract suppresses adrenocortical cancer cell proliferation through modulation of the apoptotic pathway, steroidogenesis, and insulin-like growth factor type 1 receptor/RAC-? serine/threonine-protein kinase signaling." J Med Food. 2012 Apr;15(4):325-34.
Fang, E., et al. "RNase MC2: a new Momordica charantia ribonuclease that induces apoptosis in breast cancer cells associated with activation of MAPKs and induction of caspase pathways." Apoptosis. 2012 Apr;17(4):377-87.
Guan, L. "Synthesis and anti-tumour activities of sulphated polysaccharide obtained from Momordica charantia." Nat Prod Res. 2012;26(14):1303-9
Fang, E., et al. "Momordica Charantia lectin, a type II ribosome inactivating protein, exhibits antitumor activity toward human nasopharyngeal carcinoma cells in vitro and in vivo." Cancer Prev Res (Phila). 2012 Jan;5(1):109-21.
Pitchakarn, P., et al. "Kuguacin J isolated from Momordica charantia leaves inhibits P-glycoprotein (ABCB1)-mediated multidrug resistance." J Nutr Biochem. 2012 Jan;23(1):76-84.
Ru, P., et al. "Bitter melon extract impairs prostate cancer cell-cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model." Cancer Prev Res (Phila). 2011 Dec;4(12):2122-30.
Kupradinun, P., et al. "Anticlastogenic and anticarcinogenic potential of Thai bitter gourd fruits." Asian Pac J Cancer Prev. 2011;12(5):1299-305.
Feng, E., et al. "Bitter gourd (Momordica charantia) is a cornucopia of health: a review of its credited antidiabetic, anti-HIV, and antitumor properties." Curr Mol Med. 2011 Jul;11(5):417-36. Review.
Pitchakarn, P., et al. "Induction of G1 arrest and apoptosis in androgen-dependent human prostate cancer by Kuguacin J, a triterpenoid from Momordica charantia leaf." Cancer Lett. 2011 Jul 28;306(2):142-50.
Kai, H., et al. "Inhibition of proliferation by agricultural plant extracts in seven human adult T-cell leukaemia (ATL)-related cell lines." J Nat Med. 2011 Jul;65(3-4):651-5.
Agrawal, R., et al. "Chemopreventive and anticarcinogenic effects of Momordica charantia extract." Asian Pac J Cancer Prev. 2010;11(2):371-5.
Pitchakarn, P., et al. "Momordica charantia leaf extract suppresses rat prostate cancer progression in vitro and in vivo." Cancer Sci. 2010 Oct;101(10):2234-40.
Okada, Y., et al. "Screening of dried plant seed extracts for adiponectin production activity and tumor necrosis factor-alpha inhibitory activity on 3T3-L1 adipocytes." Plant Foods Hum Nutr. 2010 Sep;65(3):225-32.
Ray, R., et al. "Bitter melon (Momordica charantia) extract inhibits breast cancer cell proliferation by modulating cell cycle regulatory genes and promotes apoptosis." Cancer Res. 2010 Mar 1;70(5):1925-31.
Rossmann, M., et al. "Eleostearic Acid inhibits breast cancer proliferation by means of an oxidation-dependent mechanism." Cancer Prev. Res. (Phila Pa). 2009; 2(10): 879-86.
Li, M., "Anti-tumor activity and immunological modification of ribosome-inactivating protein (RIP) from Momordica charantia by covalent attachment of polyethylene glycol." Acta Biochim. Biophys. Sin. (Shanghai). 2009; 41(9): 792-9.
Xiong, S., et al. "Ribosome-inactivating proteins isolated from dietary bitter melon induce apoptosis and inhibit histone deacetylase-1 selectively in premalignant and malignant prostate cancer cells." Int. J. Cancer. 2009 Aug 15; 125(4): 774-82.
Kobori, M., et al. "Alpha-eleostearic acid and its dihydroxy derivative are major apoptosis-inducing components of bitter gourd." J. Agric. Food Chem. 2008 Nov; 56(22): 10515-20.
Fan, J., et al. "Effects of recombinant MAP30 on cell proliferation and apoptosis of human colorectal carcinoma LoVo cells." Mol. Biotechnol. 2008 May; 39(1): 79-86.
Akihisa, T., et al. "Cucurbitane-type triterpenoids from the fruits of Momordica charantia and their cancer chemopreventive effects." J. Nat. Prod. 2007; 70(8):1233-9.
Khan, S., et al. "Bitter gourd (Momordica charantia): a potential mechanism in anti-carcinogenesis of colon." World J. Gastroenterol. 2007 Mar; 13(11): 1761-2.
Hwang, Y., et al. "Momordin I, an inhibitor of AP-1, suppressed osteoclastogenesis through inhibition of NF-kappaB and AP-1 and also reduced osteoclast activity and survival." Biochem. Biophys. Res. Commun. 2005 Nov; 337(3): 815-23.
Yasui, Y., et al. “Bitter gourd seed fatty acid rich in 9c,11t,13t-conjugated linolenic acid induces apoptosis and up-regulates the GADD45, p53 and PPARgamma in human colon cancer Caco-2 cells.” Prostaglandins Leukot. Essent. Fatty Acids. 2005 Aug; 73(2): 113-9.
Ike, K., et al. “Induction of interferon-gamma (IFN-gamma) and T helper 1 (Th1) immune response by bitter gourd extract.” J. Vet. Med. Sci. 2005; 67(5): 521-4.
Nagasawa, H., et al. “Effects of bitter melon (Momordica charantia) or ginger rhizome (Zingiber offifinale Rosc.) on spontaneous mammary tumorigenesis in SHN mice.” Am. J. Clin. Med. 2002; 30(2–3): 195–205.
Kim, J. H., et al. “Induction of apoptosis by momordin I in promyelocytic leukemia (HL-60) cells.” Anticancer Res. 2002 May-Jun; 22(3): 1885-9.
Tazzari, P. L., et al. “An Epstein-Barr virus-infected lymphoblastoid cell line (D430B) that grows in SCID-mice with the morphologic features of a CD30+ anaplastic large cell lymphoma, and is sensitive to anti-CD30 immunotoxins.” Haematologica. 1999; 84(11): 988-95.
Lee, D. K., et al. “Momordins inhibit both AP-1 function and cell proliferation.” Anticancer Res. 1998 Jan-Feb; 18(1A): 119-24.
Terenzi, A., et al. “Anti-CD30 (BER=H2) immunotoxins containing the type-1 ribosome-inactivating proteins momordin and PAP-S (pokeweed antiviral protein from seeds) display powerful antitumor activity against CD30+ tumor cells in vitro and in SCID mice.” Br. J. Haematol. 1996; 92(4): 872–79.
Bolognesi, A., et al. “Induction of apoptosis by ribosome-inactivating proteins and related immunotoxins.” Int. J. Cancer. 1996 Nov; 68(3): 349-55.
Battelli, M. G., et al. “Toxicity of ribosome-inactivating proteins-containing immunotoxins to a human bladder carcinoma cell line.” Int. J. Cancer. 1996 Feb; 65(4): 485-90.
Lee-Huang, S., et al. “Anti-HIV and anti-tumor activities of recombinant MAP30 from bitter melon.” Gene. 1995; 161(2):151–56.
Cunnick, J. E., et al. “Induction of tumor cytotoxic immune cells using a protein from the bitter melon (Momordica charantia).” Cell Immunol. 1990 Apr; 126(2): 278-89.
Zhu, Z. J., et al. “Studies on the active constituents of Momordica charantia l.” Yao. Hsueh. Hsueh. Pao. 1990; 25(12): 898–903.
Stirpe, F., et al. “Selective cytotoxic activity of immunotoxins composed of a monoclonal anti-Thy 1.1 antibody and the ribosome-inactivating proteins bryodin and momordin.” Br. J. Cancer. 1988 Nov; 58(5): 558-61.
Takemoto, D. J., et al. “Purification and characterization of a cytostatic factor with anti-viral activity from the bitter melon. Part 2.” Prep Biochem. 1983; 13(5): 397-421.
Takemoto, D. J., et al. “The cytotoxic and cytostatic effects of the bitter melon (Momordica charantia) on human lymphocytes.” Toxicon. 1982; 20: 593–99.
Takemoto, D. J., et al. “Guanylate cyclase activity in human leukemic and normal lymphocytes. Enzyme inhibition and cytotoxicity of plant extracts.” Enzyme. 1982; 27(3): 179–88.
Takemoto, D. J., et al. “Partial purification and characterization of a guanylate cyclase inhibitor with cytotoxic properties from the bitter melon (Momordica charantia).” Biochem. Biophys. Res. Commun. 1980; 94(1): 332–39.
Claflin, A. J., et al. “Inhibition of growth and guanylate cyclase activity of an undifferentiated prostate adenocarcinoma by an extract of the balsam pear (Momordica charantia abbreviata).” Proc. Natl. Acad. Sci. 1978; 75(2): 989–93.
Vesely, D. L., et al. “Isolation of a guanylate cyclase inhibitor from the balsam pear (Momordica charantia abbreviata).” Biochem. Biophys. Res. Commun. 1977; 77(4): 1294–99.
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. [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.
Cat’s Claw (Uncaria tomentosa)
In addition to it's long documented immune stimulant actions, cat's claw (as well as it's various alkaloids) have been documented with anticancerous actions in the following studies.* One research group has also reported cat's claw might work in a similar fashion as tamoxifen by blocking estrogen receptor sites in breast tissues.*
Santos Araújo Mdo, C., et al. "Uncaria tomentosa-Adjuvant Treatment for Breast Cancer: Clinical Trial." Evid Based Complement Alternat Med. 2012;2012:676984.
Farias, I., et al. "Uncaria tomentosa for Reducing Side Effects Caused by Chemotherapy in CRC Patients: Clinical Trial." Evid Based Complement Alternat Med. 2012;2012:892182.
Anter, J., et al. "Antigenotoxicity, cytotoxicity, and apoptosis induction by apigenin, bisabolol, and protocatechuic acid." J Med Food. 2011 Mar;14(3):276-83.
Gurrola-Díaz, C., et al. "Inhibitory mechanisms of two Uncaria tomentosa extracts affecting the Wnt-signaling pathway." Phytomedicine. 2011 Jun 15;18(8-9):683-90.
Pilarski, R., et al. "Anticancer activity of the Uncaria tomentosa (Willd.) DC. preparations with different oxindole alkaloid composition." Phytomedicine. 2010 Dec 1;17(14):1133-9.
Dreifuss, A., et al. "Antitumoral and antioxidant effects of a hydroalcoholic extract of cat's claw (Uncaria tomentosa) (Willd. Ex Roem. & Schult) in an in vivo carcinosarcoma model." J Ethnopharmacol. 2010 Jul 6;130(1):127-33
García Giménez, D., et al. "Cytotoxic effect of the pentacyclic oxindole alkaloid mitraphylline isolated from Uncaria tomentosa bark on human ewing's sarcoma and breast cancer cell lines." Planta Med. 2010 Feb; 76(2):133-6.
Rinner, B., et al. "Antiproliferative and pro-apoptotic effects of Uncaria tomentosa in human medullary thyroid carcinoma cells." Anticancer Res. 2009; 29(11): 4519-28.
Erowele, G., et al. "Pharmacology and therapeutic uses of cat's claw." Am. J. Health Syst. Pharm. 2009 Jun 1; 66(11): 992-5.
Pilarski, R., et al. "Antiproliferative activity of various Uncaria tomentosa preparations on HL-60 promyelocytic leukemia cells." Pharmacol. Rep. 2007 Sep-Oct; 59(5): 565-72.
Chen, A., et al. "Induction of apoptosis by Uncaria tomentosa through reactive oxygen species production, cytochrome c release, and caspases activation in human leukemia cells." Food Chem. Toxicol. 2007; 45(11): 2206-18.
García Prado, E., et al. "Antiproliferative effects of mitraphylline, a pentacyclic oxindole alkaloid of Uncaria tomentosa on human glioma and neuroblastoma cell lines." Phytomedicine. 2007; 14(4): 280-4.
Gonzales, G.F., 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.
De Martino, L., et al. "Proapoptotic effect of Uncaria tomentosa extracts." J. Ethnopharmacol. 2006 Aug; 107(1): 91-4.
Bacher, N., et al. "Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1-arrested and bcl-2-expressing acute lymphoblastic leukaemia cells." Br. J. Haematol. 2006 Mar; 132(5): 615-22.
Riva, L., et al. “The antiproliferative effects of Uncaria tomentosa extracts and fractions on the growth of breast cancer cell line." Anticancer Res. 2001; 21(4A): 2457–61.
Muhammad, I., et al. “Investigation of Una de Gato I. 7-Deoxyloganic acid and 15N NMR spectroscopic studies on pentacyclic oxindole alkaloids from Uncaria tomentosa." Phytochemistry. 2001; 57(5): 781–5.
Sheng, Y., et al. “Induction of apoptosis and inhibition of proliferation in human tumor cells treated with extracts of Uncaria tomentosa." Anticancer Res. 1998; 18(5A): 3363–68.
Salazar, E. L., et al. “Depletion of specific binding sites for estrogen receptor by Uncaria tomentosa." Proc. West. Pharmacol. Soc. 1998; 41(1): 123–124.
Stuppner, H., et al. “A differential sensitivity of oxindole alkaloids to normal and leukemic cell lines.” Planta Med. (1993 suppl.); 59: A583.
Rizzi, R., et al. “Mutagenic and antimutagenic activities of Uncaria tomentosa and its extracts." J. Ethnopharmacol. 1993; 38: 63–77.
Peluso, G., et al. “Effetto antiproliferativo su cellule tumorali di estrattie metaboliti da Uncaria tomentosa. Studi in vitro sulla loro azione DNA polimerasi.” 11 Congreso Italo-Peruano de Etnomedicina Andina, Lima, Peru, October 27–30, 1993, 21–2.
Rizzi, R., et al. “Bacterial cytotoxicity, mutagenicity and antimutagenicity of Uncaria tomentosa and its extracts. Antimutagenic activity of Uncaria tomentosa in humans." Premiere Colloque Européan d'Ethnopharmacologie, Metz, France, March 22–24, 1990.
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