| Autor: |
Cheol Park, Chung-ho Ryu, Byung tae Choi, Won ho Lee, Gi-young Kim, Yung hyun Choi, Dong-oh Moon |
| Předmět: |
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| Zdroj: |
Acta Pharmacologica Sinica; Mar2008, Vol. 29 Issue 3, p341-348, 8p, 5 Graphs |
| Abstrakt: |
Aim: To investigate whether subtoxic concentration of β-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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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