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Title 

Heyneanol A induces apoptosis via cytochrome c release and caspase activation in human leukemic U937 cells

Authors 

E O LeeByoung-Mog KwonG Y SongC H ChaeH M KimI S ShimK S AhnS H Kim

Publisher 

Elsevier

Issue Date 

2004

Citation 

Life Sciences, vol. 74, no. 18, pp. 2313-2326

Keywords 

apoptosiscaspasecytochrome cheyneanol APARPU937 cellsvitis amurensisZ-VAD-FMKbenzyloxycarbonylvalylalanylaspartyl fluoromethyl ketonecaspase 8

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 (IC50 = 6.6 μM at 24 h) exhibited stronger cytotoxic effect than resveratrol (IC50 = 100 μM at 24 h) by 15-fold on human leukemic U937 cells by XTT assay. Apoptotic bodies were observed in U937 cells treated with 6 μM of heyneanol A by TUNEL assay. Heyneanol A effectively increased the portion of sub-G1 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.

ISSN 

0024-3205

Link 

http://dx.doi.org/10.1016/j.lfs.2003.10.004

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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