OncoTargets and Therapy (Dec 2016)
Anticancer activities of epigallocatechin-3-gallate against cholangiocarcinoma cells
Abstract
Tae Won Kwak,1,* Su Bum Park,2,* Hyun-Jung Kim,3 Young-IL Jeong,4 Dae Hwan Kang1,2 1Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, 2Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, Gyeongnam, 3Genewel Co. Ltd. Seongnam, Gyeonggi-do, 4Biomedical Research Institute, Pusan National University Hospital, Pusan, Republic of Korea *These authors equally contributed to this work Purpose: Epigallocatechin-3-gallate (EGCG) is an antioxidant agent derived from green tea. Because it has chemopreventive and anti-invasive effect against various cancer cells, EGCG can be used to inhibit proliferation and invasion of cholangiocarcinoma (CCA) cells. Methods: The anticancer effects of EGCG were studied using human CCA cells (HuCC-T1). Apoptosis was analyzed by Western blotting. Invasion and migration of cancer cells were assessed with Matrigel® and wound healing assays. An animal tumor xenograft model of HuCC-T1 was used to study the in vivo antitumor activities of EGCG. Results: EGCG effectively inhibited the growth of HuCC-T1 cells with no adverse effects on the viability of 293T cells. EGCG induced apoptotic cell death at 5 µg/mL concentration. It inhibited the expression of mutant p53 and induced apoptotic molecular signals such as Bax/Bcl-2, Caspase, and cytochrome C. Furthermore, EGCG dose-dependently inhibited the activity of matrix metalloproteinase (MMP)-2/9, invasion, and migration. In the animal tumor xenograft model of HuCC-T1 cells, EGCG was subcutaneously administered beside the tumor for local treatment. EGCG efficiently inhibited growth of the tumor and suppressed carcinogenic molecular signals such as Notch1, MMP-2/9, and proliferating cell nuclear antigen. Conclusion: EGCG induced apoptosis of cancer cells without adverse effects on normal cells. EGCG inhibited growth, invasion, and migration of HuCC-T1 cells. We suggest EGCG as a promising candidate for local treatment of CCA. Keywords: epigallocatechin-3-gallate, cholangiocarcinoma, matrix metalloproteinases-2, invasion, thermosensitive hydrogel
