Therapeutic potential of inhibition of the NF-κB pathway in the treatment of inflammation and cancer

These results suggest that stimulation of the NF-κB pathway may be involved in the enhanced inflammatory response associated with these diseases

Yumi Yamamoto; Richard B. Gaynor

2008

Scholarcy highlights

  • NF-κB comprises a family of inducible transcription factors that serve as important regulators of the host immune and inflammatory response
  • NF-κB regulation of cellular apoptosis and proliferation In addition to activating the expression of genes involved in the control of the immune and inflammatory response, the NF-κB pathway is a key mediator of genes involved in the control of the cellular proliferation and apoptosis
  • Treatment of patients with inflammatory bowel diseases with steroids decreases NF-κB activity in biopsy specimens and reduces clinical symptoms. These results suggest that stimulation of the NF-κB pathway may be involved in the enhanced inflammatory response associated with these diseases
  • The ΙκBα super-repressor suppresses constitutive and TNF-α–induced NF-κB activity in human head and neck carcinoma cells in tissue culture and reduces the growth of such tumors in SCID mice. These results suggest that the IκBα super-repressor inhibits the expression of NFκB–dependent genes, which can enhance the growth of squamous cell carcinomas
  • Inhibition of the NF-κB pathway by immunosuppressive agents Cyclosporin A and tacrolimus are immunosuppressive agents used in organ transplantation to prevent graft-versus-host disease
  • Downregulation of the NF-κB pathway by cyclopentenone prostaglandins NF-κB regulates the expression of a variety of genes involved in the immune and inflammatory responses, including COX-2
  • It is possible that specific inhibitors of IKK activity may provide a new class of anti-inflammatory and anticancer agents or of adjunct therapeutics to enhance the efficacy of other cancer therapies

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