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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2013.1
- 수록면
- 29 - 34 (6page)
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The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor family of cytokines. TRAIL selectively induces apoptotic cell death in various tumors and cancer cells, but it has little or no toxicity in normal cells. Agonism of TRAIL receptors has been considered to be a valuable cancer-therapeutic strategy. However, more than 85% of primary tumors are resistant to TRAIL, emphasizing the importance of investigating how to overcome TRAIL resistance. In this report, we have found that nemadipine-A, a cell-permeable L-type calcium channel inhibitor, sensitizes TRAIL-resistant cancer cells to this ligand. Combination treatments using TRAIL with nemadipine-A synergistically induced both the caspase cascade and apoptotic cell death, which were blocked by a pan caspase inhibitor (zVAD) but not by autophagy or a necrosis inhibitor. We further found that nemadipine-A, either alone or in combination with TRAIL, notably reduced the expression of survivin, an inhibitor of the apoptosis protein (IAP) family of proteins. Depletion of survivin by small RNA interference (siRNA) resulted in increased cell death and caspase activation by TRAIL treatment. These results suggest that nemadipine-A potentiates TRAIL-induced apoptosis by down-regulation of survivin expression in TRAIL resistant cells. Thus, combination of TRAIL with nemadipine-A may serve a new therapeutic scheme for the treatment of TRAIL resistant cancer cells, suggesting that a detailed study of this combination would be useful.
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참고문헌 (38)
참고문헌 신청
Abdulghani, J. / 2010 / TRAIL receptor signaling and therapeutics / Expert Opin. Ther. Targets 14:1091~1108
Altieri, D. C. / 2010 / Survivin and IAP proteins in cell-death mechanisms / Biochem. J 430:199~205
Ammann, J. U. / 2009 / Sensitization of neuroblastoma cells for TRAIL-induced apoptosis by NF-kappaB inhibition / Int. J. Cancer 124:1301~1311
Bellail, A. C. / 2009 / TRAIL agonists on clinical trials for cancer therapy; the promises and the challenges / Rev. Recent Clin. Trials 4:34~41
Cho, D. H. / 2009 / Caspase-mediated cleavage of ATG6/Beclin-1 links apoptosis to autophagy in HeLa cells / Cancer Lett 274:95~100
Altieri, D. C. / 2010 / Survivin and IAP proteins in cell-death mechanisms / Biochem. J 430:199~205
Ammann, J. U. / 2009 / Sensitization of neuroblastoma cells for TRAIL-induced apoptosis by NF-kappaB inhibition / Int. J. Cancer 124:1301~1311
Bellail, A. C. / 2009 / TRAIL agonists on clinical trials for cancer therapy; the promises and the challenges / Rev. Recent Clin. Trials 4:34~41
Cho, D. H. / 2009 / Caspase-mediated cleavage of ATG6/Beclin-1 links apoptosis to autophagy in HeLa cells / Cancer Lett 274:95~100
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