Potential chemo-prophylactics effect of green tea catechins in pre-malignant and malignant prostate

Green tea catechins have been recognized as a potential chemopreventive agent for prostate. Prostatic intraepithelial neoplasia (PIN) lesion is widely accepted as the pre-invasive stage of adenocarcinoma and a predictive marker of prostate cancer development. This study confirmed that novel catechin-derivatives showed a greater inhibitory effect on proliferation in PIN cells than in PCa cells. In addition, two minor existing catechins, (-)-epigallocatechin (EGC) and (-)- epicatechin (EC) showed a synergistic inhibitory effect on PIN cell growth, invasion, migration and progression of PIN to a mesenchymal-like invasive phenotype by inhibition of Epithelial Mesenchymal Transition (EMT)-associated transcriptional factors such as Twist, Snail, Slug and Zeb-l. In this study, a carcinoma-associated fibroblast (CAF)-like human bone marrow- derived mesenchymal stem cells (hMSCs) was established via exposing hMSCs to human prostate tumour-conditioned medium (TCM). TCM-exposed hMSCs exhibited the ability to promote tumour cell growth of prostate and colon cancer and PIN cell invasion. Green tea catechin treatment inhibited PIN cell invasion by reversal of EMT. A chemo-resistant (CR) prostate cell line (CR-PC3M) was established and exhibited a greater resistance to several chemotherapeutic drugs such as 5- fluorouacil, Taxotere and Doxorubicin, and expressed a high level of a drug resistance-associated transporter ABCG2 and the cancer stem cell (CSC) markerEThOS - Electronic Theses Online ServiceGBUnited Kingdo