Catechin-vanilloid synergies with potential clinical applications in cancer





D.M. Morré and D.J. Morré

Departments of Medicinal Chemistry & Molecular Pharmacology and Foods & Nutrition, Purdue University, West Lafayette, Indiana 47907, USA



Demographics predict future increases in cancer burden as the global population grows and ages. These trends present challenges to develop and implement improved anticancer strategies with absolute cancer specificity and low or no toxicity to non-cancer cells and tissues. Our work has identified a cancer-specific cell surface protein, tNOX, as a target for low dose cell killing (apoptosis) of cancer cells by green tea catechin and Capsicum vanilloid combinations. This protein is unique in that it is associated with all forms of cancer and is absent from normal cells and tissues. Activity of tNOX is correlated with cancer growth and when blocked, cancer cells fail to enlarge following 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. By combining vector-forced overexpression of tNOX cDNA and antisense, we have demonstrated the tNOX target to be 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. The transgenic mice grew faster and the increased growth due to tNOX overexpression was blocked by EGCg provided 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 has been developed and is undergoing clinical evaluation as a therapeutic aid for cancer patients.




Key words: tNOX, cancer target, catechin-vanilloid synergies, transgenic, green tea







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