Induction of Apoptosis by Combination Treatment with Luteolin and TRAIL in T24 Human Bladder Cancer Cells

摘要

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis by targeting cancer cells. However, some cancer cells are resistant to TRAIL-induced cytotoxicity. One method of overcoming TRAIL resistance is combination treatment with reagents to sensitize cells to TRAIL. Luteolin, a flavonoid, has been shown to have anti-cancer effects by inducing apoptosis and cell cycle arrest in various cancer cell lines in vitro. In this study, we investigated the effects of combination treatment with non-toxic concentration of TRAIL and luteolin in T24 human bladder cancer cells. Combined treatment with luteolin and TRAIL significantly inhibits cell proliferation via activation of caspases by inducing Bid truncation, up-regulation of Bax and down-regulation of X-linked inhibitor of apoptosis protein (XIAP). However, the apoptotic effects of combination treatment with luteolin and TRAIL were significantly inhibited by specific caspases inhibitors. Taken together, these resultsindicate that combination treatment with TRAIL and luteolin can induce apoptosis in TRAIL-resistant cancer cells through down-regulation of XIAP and modulation of tBid and Bax expression.