A transgenic mouse line overexpressing the anticancer green tea target, tNOX, responds to EGCg

Kader Yagiz, Purdue University

Abstract

Our laboratories have identified a novel cancer-specific and growth-related cell-surface protein with protein disulfide-thiol interchange and hydroquinone (NADH) oxidase activities designated as tNOX (t&barbelow;umor-associated N&barbelow;ADH Oxidase). tNOX has been proposed as the cellular target for the anticancer action of various quinone site inhibitors with anticancer activity including the green tea polyphenol (-)-epigallocatechin-3-gailate (EGCg). A transgenic mouse line overexpressing tNOX was generated to determine its overall growth phenotype and susceptibility to EGCg. Cultured non-cancer cells lack tNOX and are unresponsive to EGCg. Overexpression of tNOX in cultured non-cancer cells through transfection resulted in both enhanced growth and an acquired inhibitory response to EGCg. The tNOX transgenic mouse line was developed using a phCMV2 vector with a HA tag. Transgenic mice exhibited both an enhanced growth rate and a response to EGCg not observed with wild type mice. Female transgenic mice grew twice as fast as wild type and growth was reflected in an overall increased carcass weight. Administration of EGCg in the drinking water (500 mg/kg body weight) reduced the growth rate of the transgenic mice to that of wild type mice. With male transgenic mice, the response to EGCg differed from that of female transgenic mice. Mouse embryonic fibroblast cells prepared from transgenic mice also grew at rates approximately twice as those of wild type embryonic cells. Growth of transgenio mouse embryonic fibroblast cells was inhibited by low concentrations of EGCg and followed after about 48 h by apoptosis. These findings provided in situ validation of the hypothesis that tNOX represents a necessary and sufficient molecular target as the basis for the protective and potential cancer therapeutic benefits of EGCg.^

Degree

Ph.D.

Advisors

Dorothy M. Morre, Purdue University.

Subject Area

Biology, Molecular|Health Sciences, Nutrition

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