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KMID : 1140120120170010037
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Cancer Prevention Research
2012 Volume.17 No. 1 p.37 ~ p.44
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Luteolin-induced Sensitization of PLC/PRF/5 Human Hepatocellular Carcinoma Cells to TRAIL-Mediated Apoptosis
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Kim Eun-Young
Kim An-Keun
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Abstract
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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.
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KEYWORD
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CANCER PREVENTION RESEARCH
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