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KMID : 1134820110400091201
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Journal of the Korean Society of Food Science and Nutrition
2011 Volume.40 No. 9 p.1201 ~ p.1207
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Induction of Apoptosis by Combined-treatment with Genistein and TRAIL in U937 Human Leukemia Cells
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Choi Yung-Hyun
Han Min-Ho
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Abstract
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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been proposed as a potent tool to trigger apoptosis in cancer therapy. However, as many types of cancer cells remain resistant towards TRAIL-induced cytotoxicity, several combined therapy approaches aimed to sensitize cells to TRAIL have been developed. Genistein, a natural isoflavonoid phytoestrogen, has been shown to have anticancer activity by inducing cell cycle arrest at G2M phase as well as apoptosis in various cancer cell lines. In the present study, we showed that treatment with TRAIL in combination with subtoxic concentrations of genistein sensitized U937 human leukemia cells to TRAIL-mediated apoptosis. Combined treatment with genistein and TRAIL effectively activated caspases through Bid truncation (tBid) and down-regulation of cellular caspase-8 (FLICE)-like inhibitory proteinL(cFLIPL). However, the apoptotic effects of co-treatment with genistein and TRAIL were significantly inhibited by specific caspase inhibitors, which demonstrates the important role of caspases in apoptosis induced by genis-tein and TRAIL. Overall, our results indicate that genistein can potentiate TRAIL-induced apoptosis through down-regulation of cFLIPL and up-regulation of pro-apoptotic tBid proteins.
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KEYWORD
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genistein, TRAIL, U937, apoptosis
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