PLC/PRF/5 인체 간암 세포에서 Luteolin에 의한 TRAIL 감수성 증가 효과

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor super family, has been expected as a promising anticancer agent because of its ability to induce apoptosis in malignant cells but not in normal cells. However, some cancer cells have resistance mechanisms to TRAIL-mediated apoptosis. Strategies to enhance potential of TRAIL are therefore needed for effective TRAIL therapy. In this study, we showed that luteolin enhances TRAIL-induced cytotoxicity in PLC/PRF/5 human hepatocellular carcinoma cells, whereas acacetin, caffeic acid phenethyl ester, quercetin produces no effect. Synergistic induction of apoptosis was confirmed by flow cytometric analysis after annexin V/PI double staining. Also, PARP-cleavage and activation of effector caspases were significantly enhanced by TRAIL/luteolin combination compared to either agent alone. Furthermore, activation of Bid and Bax/Bcl-2 ratio up-regulation were markedly enhanced as well as caspase-8 and caspase-9 activation by TRAIL/luteolin combined treatment, suggesting that both extrinsic and intrinsic apoptotic pathway are triggered in PLC/PRF/5 cells treated with TRAIL and luteolin combination.