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Beta-sitosterol sensitizes MDA-MB-231 cells to TRAIL-induced apoptosis.
- Source :
-
Acta pharmacologica Sinica [Acta Pharmacol Sin] 2008 Mar; Vol. 29 (3), pp. 341-8. - Publication Year :
- 2008
-
Abstract
- 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.<br />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.<br />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.<br />Conclusion: The synergistic treatment of SITO and TRAIL induces apoptosis, which can serve as a potential preventive and therapeutic agent.
- Subjects :
- Annexin A5 metabolism
Breast Neoplasms drug therapy
Breast Neoplasms metabolism
Cell Line, Tumor
Cell Survival drug effects
Dose-Response Relationship, Drug
Drug Synergism
Female
Fluorescein-5-isothiocyanate metabolism
Fluorescent Dyes metabolism
Formazans metabolism
Humans
Tetrazolium Salts metabolism
Apoptosis drug effects
Breast Neoplasms pathology
Hypolipidemic Agents pharmacology
Sitosterols pharmacology
TNF-Related Apoptosis-Inducing Ligand pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1745-7254
- Volume :
- 29
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Acta pharmacologica Sinica
- Publication Type :
- Academic Journal
- Accession number :
- 18298899
- Full Text :
- https://doi.org/10.1111/j.1745-7254.2008.00761.x