WYC02-9 on Colorectal Cancer: Apoptosis and Autophagy

• Main Authors: Yu-Heng Lin, 林宇姮
• Other Authors: Ming-Tsai Liang
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/71294131792877149933

碩士 === 義守大學 === 生物技術與化學工程研究所碩士班 === 99 === According to the data of Department of Health R.O.C. report, colorectal cancer (CRC) is the second leading cause of cancer death in Taiwan, and most of the cases occur after 50 old. Many chemotherapeutic agents used in clinics have high toxicity to normal tissues and cause many side-effects on patients. Therefore, it is important to search for effective and low toxic anticancer drugs for cancer therapy. WYC02 is a novel flavonoids isolated from the whole plant of T. torresiana and has a potent anticancer effect. WYC02-9, a derivative of WYC02, shows a more potent cytotoxicity than WYC02 on HCT116 colorectal cancer cells. We identified that WYC02-9 inhibited the cancer cells growth by colony formation and soft agar assays. In nude mice model, WYC02-9 had a significant anti-cancer activity against colorectal tumor growth without major side effects. Moreover, WYC02-9 arrested cell cycle progression at G2/M phase. And, WYC02-9 forced cancer cells to go through apoptosis by inducing the activity of caspase-8, caspase-9, caspase-3, and inhibiting the activity of PARP. WYC02-9 inhibited cell proliferation by promoting the activity of p38 MAPK, which was reversed by p38 MAPK inhibitor, suggesting that p38 MAPK may play a major role in WYC02-9-induced cell death. On the other hand, WYC02-9 induced LC3-Ⅱ protein, and then induced autophagy in cancer cells.