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http://dx.doi.org/10.5352/JLS.2013.23.9.1118

Effect of Proapoptotic Bcl-2 on Naringenin-induced Apoptosis in Human Leukemia U937 Cells  

Park, Cheol (Department of Molecular Biology, College of Natural Sciences, Dongeui University)
Jin, Cheng-Yun (School of Pharmaceutical Science, Zhengzhou University)
Choi, Tae Hyun (Department of Ophthalmic Optics, Daegu Technical University)
Hong, Su Hyun (Department of Biochemistry, Dongeui University College of Oriental Medicine)
Choi, Yung Hyun (Department of Biochemistry, Dongeui University College of Oriental Medicine)
Publication Information
Journal of Life Science / v.23, no.9, 2013 , pp. 1118-1125 More about this Journal
Abstract
Naringenin, a naturally occurring citrus flavonone, is a potentially valuable candidate for cancer chemotherapy. However, the cellular and molecular mechanisms responsible for its anticancer activity are largely unknown. In the present study, we attempted to elucidate the mechanisms responsible for naringenin-induced apoptosis in human leukemic U937 cells. We found that naringenin markedly inhibited the growth of U937 cells by decreasing cell proliferation and inducing apoptosis, which was associated with the activation of caspases. A pan-caspase inhibitor, z-VAD-fmk, significantly inhibited naringenin-induced U937 cell apoptosis, indicating that caspases are key regulators of apoptosis in response to naringenin in U937 cells. Although the levels of antiapoptotic Bcl-2 and proapoptotic Bax proteins remained unchanged in naringenin-treated U937 cells, Bcl-2 overexpression attenuated naringenin-induced apoptosis. Furthermore, combined treatment with naringenin and HA14-1, a small-molecule Bcl-2 inhibitor, effectively increased the apoptosis through enhancement of XIAP down-regulation, Bid cleavage, and caspase activation, suggesting that the synergistic effect was at least partially mediated through the death receptor-mediated apoptosis pathway.
Keywords
Naringenin; U937 cells; apoptosis; Bcl-2; caspase;
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