The Roles of p53 and Securin on Fisetin-induced Apoptosis in Human Colorectal Cancer Cells

• Main Authors: Sz-Hsien Yu, 余思賢
• Other Authors: Shu-Jun Chiu
• Format: Others
• Language: zh-TW
• Online Access: http://ndltd.ncl.edu.tw/handle/69738458067564171609

碩士 === 慈濟大學 === 生命科學研究所 === 97 === Securin, also known as pituitary tumor transforming gene (PTTG), is highly expressed in various cancer cells and regulates cancer cell proliferation. Fisetin, a novel dietary flavonoid, has been shown to exert anticancer activity. However, roles of securin on the fisetin-induced apoptosis remain unknown. In this study, we found fisetin significantly diminished the securin protein expression and decreased cell survival in human colorectal cancer cells. Fisetin induced more DNA damage, apoptosis and survival inhibition in securin-null HCT116 cells than securin-wild type cells. p53, a key tumor suppressor, controls cell cycle arrest and apoptosis in cancer cells. The colorectal cancer cells with p53-wild type exhibited higher susceptibility to fisetin than p53-null cells. The caspase 3 activation and poly (ADP-ribose) polymerase cleavage were induced by fisetin in p53-wild type colorectal cancer cells, but not in the p53-null cells. In addition, fisetin downregulated securin via a p53-dependent pathway in colorectal cancer cells. Furthermore, knockdown of securin proteins increased fisetin-induced apoptosis in both p53-wild type and -null cells. Taken together, securin plays an important role on the fisetin-induced DNA damage and apoptosis in human colorectal cancer cells. Loss of securin expression may impair cellular DNA repair ability, hence, enhances fisetin-induced apoptosis and survival inhibition in human colorectal cancre cells regardless of functional p53 expression.