Heyneanol A induces apoptosis via cytochrome c release and caspase activation in human leukemic U937 cells |
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Authors: | Lee Eun-Ok Kwon Byoung-Mog Song Gyu-Yong Chae Chan-Hee Kim Hyung-Min Shim In-Sop Ahn Kyoo-Seok Kim Sung-Hoon |
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Institution: | Department of Oncology, Graduate School of East-West Medical Science, Kyung Hee University, 1 Seochunri, Kiheungeup, Yongin 449-701, South Korea. sungkim7@khu.ac.kr |
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Abstract: | Heyneanol A, a tetramer of resveratrol, is isolated from the roots of Vitis amurensis by cytotoxicity based fractionation. In this study, the mechanism of apoptosis by heyneanol A was evaluated in human leukemic U937 cells. Heyneanol A (IC(50) = 6.6 microM at 24 h) exhibited stronger cytotoxic effect than resveratrol (IC(50) = 100 microM at 24 h) by 15-fold on human leukemic U937 cells by XTT assay. Apoptotic bodies were observed in U937 cells treated with 6 microM of heyneanol A by TUNEL assay. Heyneanol A effectively increased the portion of sub-G(1) DNA content in a time- and concentration-dependent manner by flow cytometric analysis. Heyneanol A also induced cytochrome c release from mitochondria into the cytosol and subsequent caspase activation involving caspase 9 and 3 to cleave PARP. However, it did not affect the expressions of Bax and Bcl-2 by western blotting. It was confirmed that the activation of caspase 8, 9 and 3 and the cleavage of PARP by heyneanol A were completely blocked by adding Z-VAD-FMK, a caspase inhibitor. These findings suggest that heyneanol A has anti-tumor activity, which may be mediated by apoptosis caused by cytochrome c release and caspase activation in human leukemic U937 cells. |
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Keywords: | Heyneanol A Vitis amurensis Apoptosis U937 cells Caspase PARP Cytochrome c Z-VAD-FMK |
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