title: Sensitization to docetaxel in prostate cancer cells by green tea and quercetin.
abstract: Chemotherapy with docetaxel (Doc) is a standard treatment for metastatic and castration-resistant prostate cancer. However, chemoresistance and side effects of Doc limit its clinical success. We investigated whether natural products green tea (GT) and quercetin (Q), a flavonoid from apples and onions, will enhance the efficacy of Doc in androgen-independent (AI) prostate cancer cells. Two cell lines including LAPC-4-AI and PC-3 were treated in vitro with 40 μM of (-)-epigallocatechin gallate (EGCG), 5 μM of Q, 2 or 5 nM of Doc alone or in combination. The mixture of EGCG+Q+Doc increased the antiproliferative effect by threefold in LAPC-4-AI cells and eightfold in PC-3 cells compared to Doc alone. EGCG, Q and Doc in combination significantly enhanced cell cycle arrest at G2/M phase and increased apoptosis in both LAPC-4-AI and PC-3 cells compared to Doc alone. The mixture increased the inhibition of PI3K/Akt and the signal transducer and activator of transcription (Stat) 3 signaling pathways compared to Doc alone, and decreased the protein expression of multidrug resistance-related protein. In addition, the combination with EGCG and Q increased the inhibition of tumor cell invasion and colony formation in both LAPC-4-AI and PC-3 cells compared to Doc alone, and decreased the percentage of CD44(+)/CD24(-) stem-like LAPC-4-AI cells. In summary, GT and Q enhanced the therapeutic effect of Doc in castration-resistant prostate cancer cells through multiple mechanisms including the down-regulation of chemoresistance-related proteins. This study provides a novel therapeutic modality to enhance the efficacy of Doc in a nontoxic manner.
authors: Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA; Center for Human Nutrition, University of California, Los Angeles, CA 90095, USA. Electronic address: piwenwang@cdrewu.edu.
authors: Piwen
authors: P
authors: Wang
authors: Center for Human Nutrition, University of California, Los Angeles, CA 90095, USA.
authors: Susanne M
authors: SM
authors: Henning
authors: Center for Human Nutrition, University of California, Los Angeles, CA 90095, USA.
authors: David
authors: D
authors: Heber
authors: Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA; David Geffen School of Medicine, University of California, Los Angeles, CA, USA 90095.
authors: Jaydutt V
authors: JV
authors: Vadgama
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D015536:Down-Regulation; D004357:Drug Synergism; D006801:Humans; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology*; D043823:Taxoids / Q000494:pharmacology*; D013662:Tea / Q000737:chemistry*
chemical_list: D043823:Taxoids; D013662:Tea; D000077143:Docetaxel; D002392:Catechin; D011794:Quercetin; C045651:epigallocatechin gallate; D019869:Phosphatidylinositol 3-Kinases
keywords: Combination; Docetaxel; Green tea polyphenol; Prostate cancer; Quercetin
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