Reduction of TRAIL-induced Mcl-1 and cIAP2 by c-Myc or sorafenib sensitizes resistant human cancer cells to TRAIL-induced death - PubMed (original) (raw)

doi: 10.1016/j.ccr.2007.05.006.

Seok-Hyun Kim, Kazuhiro Ogi, John P Plastaras, Jianhua Ling, Wenge Wang, Zhaoyu Jin, Yingqiu Y Liu, David T Dicker, Paul J Chiao, Keith T Flaherty, Charles D Smith, Wafik S El-Deiry

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• PMID: 17613437
• DOI: 10.1016/j.ccr.2007.05.006

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Reduction of TRAIL-induced Mcl-1 and cIAP2 by c-Myc or sorafenib sensitizes resistant human cancer cells to TRAIL-induced death

M Stacey Ricci et al. Cancer Cell. 2007 Jul.

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Abstract

Cells expressing oncogenic c-Myc are sensitized to TNF superfamily proteins. c-Myc also is an important factor in determining whether a cell is sensitive to TRAIL-induced apoptosis, and it is well established that the mitochondrial pathway is essential for apoptosis induced by c-Myc. We investigated whether c-Myc action on the mitochondria is required for TRAIL sensitivity and found that Myc sensitized cells with defective intrinsic signaling to TRAIL. TRAIL induced expression of antiapoptotic Mcl-1 and cIAP2 through activation of NF-kappaB. Both Myc and the multikinase inhibitor sorafenib block NF-kappaB. Combining sorafenib with TRAIL in vivo showed dramatic efficacy in TRAIL-resistant tumor xenografts. We propose the combination of TRAIL with sorafenib holds promise for further development.

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Comment in

• Clearing the TRAIL for Cancer Therapy.
  Hall MA, Cleveland JL. Hall MA, et al. Cancer Cell. 2007 Jul;12(1):4-6. doi: 10.1016/j.ccr.2007.06.011. Cancer Cell. 2007. PMID: 17613431 Review.

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