TY - JOUR AU - Park Cheol AU - Moon Dong-oh AU - Ryu Chung-ho AU - Choi Byung tae AU - Lee Won ho AU - Kim Gi-young AU - Choi Yung hyun PY - 2016 TI - β-Sitosterol sensitizes MDA-MB-231 cells to TRAIL-induced apoptosis JF - Acta Pharmacologica Sinica; Vol 29, No 3 (March 2008): Acta Pharmacologica Sinica Y2 - 2016 KW - N2 - 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. UR - http://www.chinaphar.com/article/view/5517