%0 Journal Article %T β-Sitosterol sensitizes MDA-MB-231 cells to TRAIL-induced apoptosis %A Park Cheol %A Moon Dong-oh %A Ryu Chung-ho %A Choi Byung tae %A Lee Won ho %A Kim Gi-young %A Choi Yung hyun %J Acta Pharmacologica Sinica %D 2016 %B 2016 %9 %! β-Sitosterol sensitizes MDA-MB-231 cells to TRAIL-induced apoptosis %K %X 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. %U http://www.chinaphar.com/article/view/5517 %V 29 %N 3 %P 341–348 %@ 1745-7254