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KMID : 1140120070120020128
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Cancer Prevention Research
2007 Volume.12 No. 2 p.128 ~ p.135
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Induction of Growth Inhibition and Apoptosis by β-sitosterol is Associated with S Phase Arrest and Down-regulation of XIAP in Human Leukemic Cells
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Park Cheol
Choi Byung-Tae
Lee Won-Ho
Kim Ki-Young
Choi Yung-Hyun
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Abstract
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Phytosterols are enriched in legumes, oil seeds and unrefined plant oils as found in foods such as peanut butter, pistachios and sunflower seeds. Previous results indicated that β-sitosterol, a most abundant phytosterol, induce growth arrest and apoptosis of several specific types of tumor cells in vitro and decreases the size and the extent of tumor metastases in vivo. However, the mechanism by which β-sitosterol induces anti-proliferation is not completely understood. This study investigated the mechanism of anti-proliferation induced by β-sitosterol in human leukemic U937 cells. Treatment of U937 cells to β-sitosterol resulted in the growth inhibition and morphological change in a dose-dependent manner. Flow cytometric analysis revealed that β-sitosterol treatment caused S phase arrest of the cell cycle and increased populations of apoptotic-sub G1 phase. β-sitosterol induced apoptosis through down-regulation
of inhibited X-linked inhibitor of apoptosis (XIAP) expression without alteration Bcl-2 family. ZDEVD-fmk, caspase-3 specific inhibitor, increased the survival rate of β-sitosterol-treated U937 cells. Although β-sitosterol did not alter Bcl-2 family, Bcl-2 overexpression cells blocked the decrease of XIAP expression. These results show that β-sitosterol potently induces S arrest and apoptosis in U937 cells, and β-sitosterol-induced apoptosis is related to the down-regulation of XIAP. And β-sitosterol can be used as a new therapeutic approach for the treatment of human monocytic leukemia cells. (Cancer Prev Res 12, 128-135, 2007)
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KEYWORD
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β-sitosterol, Cell cycle, Apoptosis, XIAP
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