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Research Paper
Bypass NF-κB-Mediated Survival Pathways by TRAIL and Smac
Xiaoyang Ren, Zhengming Xu, Jeffery N. Myers and Xiangwei Wu
volume 6 | issue 7
July 2007Pages: 1031 - 1035
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Activation of NF-κB is frequently associated with human malignancies. The involvement of NF-κB is in part attributed to its ability to activate various genes promoting cell survival. This property contributes to aggressive tumor growth and resistance to chemotherapy and radiation in cancer treatment. Various reports have shown that inhibition of NF-⎢B promotes apoptosis and suppress tumor growth. However, NF-⎢B has many important cellular functions and targeting NF-⎢B directly may lead to severe side effects. Thus, developing strategies with low cytotoxicity to overcome NK-κB-mediated cell survival is critical to improve cancer therapy. In this report, we described an approach using TRAIL/Apo2L (TNF-related apoptosis-inducing ligand TRAIL or Apo2 ligand) and a Smac analog to overcome and bypass NF-⎢B activation in cancer treatment. We have shown that a panel of head and neck squamous cell carcinoma (HNSCC) cell lines are highly resistant to TRAIL-induced apoptosis due to activation of NF-κB-mediated cell survival pathways, and that inhibition of NF-κB renders HNSCC cells sensitive to TRAIL. We further show that TRAIL and a small molecule mimic of Smac overcome and bypass NF-⎢B activation in inducing cancer cell death. Since this treatment has no effect on NF-⎢B activation and TRAIL offers tumor selectivity, co-treatment of TRAIL and Smac provides a strategy with potentially low toxicity to overcome NF-⎢B activation in cancer cells, which has potential therapeutic benefit.
Authors
Xiaoyang Ren
Baylor College of Medicine, Houston, TX
Zhengming Xu
Baylor College of Medicine, Houston, TX
Jeffery N. Myers
not setUniversity of Texas MD Anderson Cancer Center, Houston, TX USA
Xiangwei Wu
Baylor College of Medicine, Houston, TX
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.