BETA.-Sitosterol Induces Anti-proliferation and Apoptosis in Human Leukemic U937 Cells through Activation of Caspase-3 and Induction of Bax/Bcl-2 Ratio
| Autor: | Yung Hyun Choi, Cheol Park, Gi-Young Kim, Byung Tae Choi, Dong-Oh Moon, Wonho Lee, Chung-Ho Rhu |
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| Rok vydání: | 2007 |
| Předmět: |
Poly ADP ribose polymerase
Pharmaceutical Science Apoptosis Caspase 3 Inhibitor of apoptosis polycyclic compounds Humans Cell Proliferation bcl-2-Associated X Protein Pharmacology U937 cell Phospholipase C Chemistry Intrinsic apoptosis U937 Cells General Medicine Caspase Inhibitors Sitosterols Molecular biology Cell biology Enzyme Activation Proto-Oncogene Proteins c-bcl-2 UVB-induced apoptosis lipids (amino acids peptides and proteins) |
| Zdroj: | Biological and Pharmaceutical Bulletin. 30:1317-1323 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.30.1317 |
| Popis: | Beta-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 beta-sitosterol induces apoptosis is not completely understood in leukemic cells. This study investigated the mechanism of apoptosis induced by beta-sitosterol in human leukemic U937 cells. beta-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 beta-sitosterol was associated with down-regulation of Bcl-2, degradation of poly-(ADP-ribose) polymerase (PARP) and phospholipase C (PLC)-gamma1 protein, and activation of caspase-3. beta-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 beta-sitosterol-induced apoptosis. This suggests that caspase-3 activation is partially essential for beta-sitosterol-induced apoptosis. Bcl-2 overexpression also significantly blocked caspase-3 activation and the decrease in PARP cleavage by beta-sitosterol, and effectively attenuated the apoptotic response to beta-sitosterol. These results show that beta-sitosterol potently induces apoptosis in U937 cells and that beta-sitosterol-induced apoptosis is related to the selective activation of caspase-3 and induction of Bax/Bcl-2 ratio. |
| Databáze: | OpenAIRE |
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