| Beta-sitosterol sensitizes MDA-MB-231 cells to TRAIL-induced apoptosis. | |
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MedLine Citation:
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PMID: 18298899 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIM: To investigate whether subtoxic concentration of beta-sitosterol (SITO) combined with TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in TRAIL-resistant MDA-MB-231 breast cancer cells. METHODS: Cell viability and growth were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphnyl-2H-tetrazolim bromide assays, chromatin condensation, release of lactate dehydrogenase (LDH), and Annexin V+ cells. The apoptosis-related proteins were detected by Western blotting. RESULTS: Treatment with TRAIL in combination with subtoxic concentrations of SITO sensitized MDA-MB-231 breast cancer cells to TRAIL-mediated apoptosis. The synergistic treatment induced chromatin condensation, DNA fragmentation, the release of LDH, and Annexin V+ cells. The indicators of apoptosis are correlated to the induction of caspase activities, which results in the cleavage of poly(ADP-ribose)polymerase. Both the cytotoxic effects and apoptotic characteristics induced by the synergistic treatment were significantly inhibited by a pan-caspase inhibitor z-VAD-fmk, demonstrating the important role of caspases. These results indicate that caspases are crucial regulators of apoptosis induced by the combined treatment of SITO and TRAIL in MDA-MB-231 cells. CONCLUSION: The synergistic treatment of SITO and TRAIL induces apoptosis, which can serve as a potential preventive and therapeutic agent. |
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Authors:
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Cheol Park; Dong-oh Moon; Chung-ho Ryu; Byung tae Choi; Won ho Lee; Gi-young Kim; Yung hyun Choi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Acta pharmacologica Sinica Volume: 29 ISSN: 1745-7254 ISO Abbreviation: Acta Pharmacol. Sin. Publication Date: 2008 Mar |
Date Detail:
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Created Date: 2008-02-26 Completed Date: 2009-04-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100956087 Medline TA: Acta Pharmacol Sin Country: China |
Other Details:
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Languages: eng Pagination: 341-8 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Annexin A5
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metabolism Antilipemic Agents / pharmacology* Apoptosis / drug effects* Breast Neoplasms / drug therapy, metabolism, pathology* Cell Line, Tumor Cell Survival / drug effects Dose-Response Relationship, Drug Drug Synergism Female Fluorescein-5-isothiocyanate / metabolism Fluorescent Dyes / metabolism Formazans / metabolism Humans Sitosterols / pharmacology* TNF-Related Apoptosis-Inducing Ligand / pharmacology* Tetrazolium Salts / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Annexin A5; 0/Antilipemic Agents; 0/Fluorescent Dyes; 0/Formazans; 0/Sitosterols; 0/TNF-Related Apoptosis-Inducing Ligand; 0/TNFSF10 protein, human; 0/Tetrazolium Salts; 23305-68-2/MTT formazan; 3326-32-7/Fluorescein-5-isothiocyanate; 5779-62-4/sitosterol |
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