Open Accessβ‐Sitosterol sensitizes MDA‐MB‐231 cells to TRAIL‐induced apoptosis 1
Author(s) -
PARK Cheol,
MOON Dongoh,
RYU Chungho,
CHOI Byung tae,
LEE Won ho,
KIM Giyoung,
CHOI Yung hyun
Publication year - 2008
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2008.00761.x
Subject(s) - apoptosis , annexin , dna fragmentation , poly adp ribose polymerase , caspase , chemistry , microbiology and biotechnology , cancer cell , intrinsic apoptosis , fragmentation (computing) , cytotoxic t cell , lactate dehydrogenase , cancer research , programmed cell death , biology , biochemistry , medicine , cancer , dna , in vitro , polymerase , enzyme , ecology
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.