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http://dx.doi.org/10.5352/JLS.2009.19.2.249

Esculetin Induces Apoptosis through Caspase-3 Activation in Human Leukemia U937 Cells  

Park, Cheol (Blue-Bio Industry RIC, Dong-Eui University)
Hyun, Sook-Kyung (Blue-Bio Industry RIC, Dong-Eui University)
Shin, Woo-Jin (Departments of Physiology, College of Oriental Medicine, Dong-Eui University)
Chung, Kyung-Tae (Blue-Bio Industry RIC, Dong-Eui University)
Choi, Byung-Tae (Division of Meridian and Structural Medicine, School of Oriental Medicine, Pusan National University)
Kwon, Hyun-Ju (Blue-Bio Industry RIC, Dong-Eui University)
Hwang, Hye-Jin (Blue-Bio Industry RIC, Dong-Eui University)
Kim, Byung-Woo (Blue-Bio Industry RIC, Dong-Eui University)
Park, Dong-Il (Departments of Physiology, College of Oriental Medicine, Dong-Eui University)
Lee, Won-Ho (Department of Biology, College of Natural Sciences, Pusan National University)
Choi, Yung-Hyun (Blue-Bio Industry RIC, Dong-Eui University)
Publication Information
Journal of Life Science / v.19, no.2, 2009 , pp. 249-255 More about this Journal
Abstract
Esculetin, a coumarin compound, has been known to inhibit proliferation and induce apoptosis in several types of human cancer cells. However, the molecular mechanisms involved in esculetin-induced apoptosis are still uncharacterized in human leukemia cells. In this study, we have investigated whether esculetin exerts anti-proliferative and apoptotic effects on human leukemia U937 cells. It was found that esculetin could inhibit cell viability in a time-dependent manner, which was associated with the induction of apoptotic cell death such as increased populations of apoptotic- sub G1 phase. Apoptosis of U937 cells by esculetin was associated with an inhibition of Bcl-2/Bax binding activity, formation of tBid, down-regulation of X-linked inhibitor of apoptotic protein (XIAP) expression, and up-regulation of death receptor 4 (DR4) and FasL expression. Esculetin treatment also induced the degradation of ${\beta}$-catenin and DNA fragmentation factor 45/inhibitor of caspase-activated DNase (DFF45/ICAD). Furthermore, a caspase-3 specific inhibitor, z-DEVD-fmk, significantly inhibited sub-G1 phase DNA content, morphological changes and degradation of ${\beta}$-catenin and DEE45/ICAD. These results indicated that a key regulator in esculetin-induced apoptosis was caspase-3 in human leukemia U937 cells.
Keywords
Esculetin; U937; apoptosis; caspase-3;
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