The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelial-mesenchymal transition

Our data indicate that human prostate cancer cell lines contain a small population of CD44+CD133+ cancer stem cells and their self-renewal capacity is inhibited by EGCG. Furthermore, EGCG inhibits the self-renewal capacity of CD44+α2β1+CD133+ CSCs isolated from human primary prostate tumors, as measured by spheroid formation in suspension. EGCG induces apoptosis by activating capase-3/7 and inhibiting the expression of Bcl-2, survivin and XIAP in CSCs. Furthermore, EGCG inhibits epithelial-mesenchymal transition by inhibiting the expression of vimentin, slug, snail and nuclear β-catenin, and the activity of LEF-1/TCF responsive reporter, and also retards CSC's migration and invasion, suggesting the blockade of signaling involved in early metastasis. Interestingly, quercetin synergizes with EGCG in inhibiting the self-renewal properties of prostate CSCs, inducing apoptosis, and blocking CSC's migration and invasion. These data suggest that EGCG either alone or in combination with quercetin can eliminate cancer stem cell-characteristics.Since carcinogenesis is a complex process, combination of bioactive dietary agents with complementary activities will be beneficial for prostate cancer prevention and/ortreatment.Prostate cancer currently accounts for 29 percent of all new cancer diagnoses in men. It is estimated that more than 27,000 U.S. men died of this disease in 2009, and this incidence is likely to increase as the male population ages [1,2]. The development and progression of prostate cancer is a slow and complex process that involves multiple steps of tumorigenic transformation differentially modulated by endocrine, nutritional and perhaps inflammatory/immune factors. To date, the molecular mechanisms that mediate the initiation and progression of prostate cancer remain poorly understood. Preventive strategies for prostate cancer require considerable new knowledge about the mechanisms underlying the pathogenesis and progression of the disease. Cancer stem cells