Targeting CWR22Rv1 prostate cancer cell proliferation and gene expression by combinations of the phytochemicals EGCG, genistein and quercetin.
Prostate cancer (CaP) is a significant cause of death in American men. While men residing in Asia show a lower incidence of hormone-refractory prostate cancer (HRPC) compared to Caucasian males, Asian men who move to and live in the United States and adopt a western lifestyle have HRPC rates indistinguishable from Caucasian males. These findings suggest that Asian diets contain ingredients that might protect against the development of HRPC. The identity and mechanisms of such HRPC protective agents remain to be elucidated. An Asian diet may confer protection against HRPC owing to functional synergy between bioactive dietary agents, thus broadening the chemopreventive index, with increased distinct anticancer properties and decreased untoward effects. Here, whether or not a combination of epigallocatechin gallate (EGCG), genistein and quercetin, phytochemicals present in a traditional Asian diet, might exert synergy in controlling proliferation and gene expression was investigated in CWR22Rv1 CaP cells, an in vitro model mimicking CaP transition from AD (androgen dependence) to HRPC. Cell proliferation was inhibited approximately 40%, approximately 15% and approximately 20%, respectively by 2.5 microM EGCG, genistein and quercetin used alone. The co-administration of 2.5 microM of these phytochemicals suppressed proliferation synergistically in the CWR22Rv1 cells maintained in RPMI-1640 supplemented with 10% fetal bovine serum, but not in the cells maintained as serum-free cultures. Synergy in the expression of androgen receptor, tumor suppressor p53 and detoxification enzyme quinone reductase type 1, denoted NQO1, was also observed for the combined phytochemicals. These results demonstrate the feasibility of developing a diet-based combinatorial approach for CaP prevention and treatment and raise the possibility that serum added to culture medium might affect uptake, bioavailability and biological efficacy of dietary phytochemicals.
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
Tze-Chen
TC
Hsieh
Joseph M
JM
Wu
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D016895:Culture Media, Serum-Free; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D014411:Neoplastic Stem Cells / Q000187:drug effects; D008517:Phytotherapy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011794:Quercetin / Q000008:administration & dosage / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
D016895:Culture Media, Serum-Free; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002392:Catechin; D011794:Quercetin; C045651:epigallocatechin gallate; D019833:Genistein