title: Catechin-vanilloid synergies with potential clinical applications in cancer.
abstract: A cancer-specific cell surface protein, tNOX, has been identified as a target for low-dose cell killing (apoptosis) of cancer cells by green tea catechins and Capsicum vanilloid combinations. This protein is uniquely associated with all forms of cancer and is absent from normal cells and tissues. Its activity is correlated with cancer growth. When blocked, cancer cells fail to enlarge after division and eventually die. Among the most potent and effective inhibitors of tNOX are naturally occurring polyphenols exemplified by the principal green tea catechin (-)-epigallocatechin gallate (EGCg) and the vanilloid capsaicin. Catechin-vanilloid combinations are 10 to 100 times more effective than either catechins or vanilloids alone. Vector-forced overexpression of tNOX cDNA and antisense has demonstrated that the tNOX target is both necessary and sufficient to explain the anticancer properties of green tea catechins alone and in vanilloid-containing combinations. The necessity and sufficiency of tNOX was validated as the catechin target with transgenic mice overexpressing the processed form of tNOX. Transgenic mice grew faster and the increased growth caused by tNOX overexpression was blocked by EGCg in the drinking water. A catechin-vanilloid mixture where one 350-mg capsule is equivalent to 16 cups of green tea in its ability to inhibit tNOX and growth of cancer cells in culture is undergoing clinical evaluation as a therapeutic aid for cancer patients.
authors.affiliation: Department of Foods and Nutrition, Purdue University, West Lafayette, Indiana 47907-2059, USA. morredm@purdue.edu
authors.forename: Dorothy M
authors.initials: DM
authors.lastname: Morré
authors.forename: D James
authors.initials: DJ
authors.lastname: Morré
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D028241:Camellia sinensis; D002211:Capsaicin / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004357:Drug Synergism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009097:Multienzyme Complexes / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; C502158:Capsibiol-T; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D010936:Plant Extracts; D002392:Catechin; C045651:epigallocatechin gallate; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; C431909:tumor-associated NADH oxidase; D002211:Capsaicin