β-Sitosterol Induces Anti-proliferation and Apoptosis in Human Leukemic U937 Cells through Activation of Caspase-3 and Induction of Bax/Bcl-2 Ratio(Miscellaneous)
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概要
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β-Sitosterol is the main dietary phytosterol found in plants and has been shown to inhibit proliferation and induce apoptosis in human solid tumors such as colon and breast cancers. However, the mechanism by which β-sitosterol induces apoptosis is not completely understood in leukemic cells. This study investigated the mechanism of apoptosis induced by β-sitosterol in human leukemic U937 cells. β-Sitosterol induced cytotoxicity and apoptosis in U937 cells in a concentration dependent manner, as measured by hemocytometer counts, fluorescence microscopy, agarose gel electrophoresis, and flow cytometry analysis. The increase in apoptosis induced by β-sitosterol was associated with down-regulation of Bcl-2, degradation of poly-(ADP-ribose) polymerase (PARP) and phospholipase C (PLC)-γl protein, and activation of caspase-3. β-Sitosterol induced apoptosis was not associated with changes in the expression of Bcl-xL, Bax, or inhibitor of apoptosis proteins (IAPs). z-DEVD-fmk, a caspase-3 specific inhibitor, blocked caspase-3 activation and PARP degradation, and significantly attenuated β-sitosterol-induced apoptosis. This suggests that caspase-3 activation is partially essential for β-sitosterol-induced apoptosis. Bcl-2 overexpression also significantly blocked caspase-3 activation and the decrease in PARP cleavage by β-sitosterol, and effectively attenuated the apoptotic response to β-sitosterol. These results show that β-sitosterol potently induces apoptosis in U937 cells and that β-sitosterol-induced apoptosis is related to the selective activation of caspase-3 and induction of Bax/Bcl-2 ratio.
- 公益社団法人日本薬学会の論文
- 2007-07-01
著者
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MOON Dong-Oh
Faculty of Applied Marine Science, Cheju National University
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KIM Gi-Young
Faculty of Applied Marine Science, Cheju National University
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Lee Won
Department of Internal Medicine, institute of Medical Research, Sungkyunkwan University School of Me
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PARK Cheol
Department of Diagnostic Pathology, Samsung Medical Center, Sungkyunkwan University School of Medici
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Moon Dong-oh
Faculty Of Applied Marine Science Cheju National University
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Kim Gi-young
Faculty Of Applied Marine Science Cheju National University
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Choi Byung
Department Of Pediatrics St Mary's Hospital The Catholic University Of Korea
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RHU Chung-Ho
Division of Applied Life Science, Gyeongsang National University
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CHO Yung
Departments of Biochemistry, Dongeui University, College of Oriental Medicine
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Park Cheol
Department Of Diagnostic Pathology Samsung Medical Center Sungkyunkwan University School Of Medicine
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Choi Byung
Department Of Civil Engineering Sungkyunkwan University
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Lee Won
Department Of Agricultural And Biological Engineering University Of Florida
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Cho Yung
Departments Of Biochemistry Dongeui University College Of Oriental Medicine
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Choi Byung
Departments Of Anatomy Dongeui University College Of Oriental Medicine:department Of Biomaterial Con
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Rhu Chung-ho
Division Of Applied Life Science Gyeongsang National University
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Lee Won
Department Of Biology (bk21 Program) Pusan National University
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Park Cheol
Departments Of Biochemistry Dongeui University College Of Oriental Medicine:department Of Biology (b
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