Genistein sensitizes TRAIL-resistant human gastric adenocarcinoma AGS cells through activation of caspase-3 |
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Authors: | Jin Cheng-Yun Park Cheol Cheong JaeHun Choi Byung Tae Lee Tae Ho Lee Jae-Dong Lee Won Ho Kim Gi-Young Ryu Chung Ho Choi Yung Hyun |
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Institution: | Department of Biological Sciences, Pusan National University, Busan 609-735, Republic of Korea. |
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Abstract: | The cytotoxic effect of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is limited in some cancer cells, including AGS gastric adenocarcinoma cells. However, treatment with TRAIL in combination with subtoxic concentrations of genistein sensitizes TRAIL-resistant AGS cells to TRAIL-mediated apoptosis. Combined treatment with genistein and TRAIL-induced chromatin condensation and sub-G1 phase DNA content. These indicators of apoptosis are correlated with the activation of death receptors (DR5) and induction of caspase-3 activity, which results in the cleavage of poly(ADP-ribose)polymerase. Both the cytotoxic effect and apoptotic characteristics induced by combined treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrates the important role of caspase-3 in the observed cytotoxic effect. These results indicate that caspase-3 is a key regulator of apoptosis in response to combined genistein and TRAIL in human gastric adenocarcinoma AGS cells through the activation of DR5 and mitochondrial dysfunction. |
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