1. Sensitization to docetaxel in prostate cancer cells by green tea and quercetin
- Author
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Jaydutt V. Vadgama, David Heber, Susanne M. Henning, and Piwen Wang
- Subjects
Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Down-Regulation ,Apoptosis ,Docetaxel ,Biochemistry ,Article ,Catechin ,Phosphatidylinositol 3-Kinases ,Prostate cancer ,Cell Line, Tumor ,Internal medicine ,medicine ,Humans ,Molecular Biology ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Nutrition and Dietetics ,Tea ,biology ,Cell growth ,CD44 ,Prostatic Neoplasms ,Drug Synergism ,Cell Cycle Checkpoints ,medicine.disease ,Endocrinology ,Cell culture ,biology.protein ,Cancer research ,Quercetin ,Taxoids ,medicine.drug - 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. more...
- Published
- 2015
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