Curcumin modulates the radiosensitivity of colorectal cancer cells by suppressing constitutive and inducible NF-kappaB activity

Int J Radiat Oncol Biol Phys. 2009 Oct 1;75(2):534-42. doi: 10.1016/j.ijrobp.2009.06.034.


Purpose: Radiation therapy is an integral part of the preoperative treatment of rectal cancers. However, only a minority of patients achieve a complete pathologic response to therapy because of resistance of these tumors to radiation therapy. This resistance may be mediated by constitutively active pro-survival signaling pathways or by inducible/acquired mechanisms in response to radiation therapy. Simultaneous inhibition of these pathways can sensitize these tumors to radiation therapy.

Methods and materials: Human colorectal cancer cells were exposed to clinically relevant doses of gamma rays, and the mechanism of their radioresistance was investigated. We characterized the transcription factor nuclear factor-kappaB (NF-kappaB) activation as a mechanism of inducible radioresistance in colorectal cancer and used curcumin, the active ingredient in the yellow spice turmeric, to overcome this resistance.

Results: Curcumin inhibited the proliferation and the post-irradiation clonogenic survival of multiple colorectal cancer cell lines. Radiation stimulated NF-kappaB activity in a dose- and time-dependent manner, whereas curcumin suppressed this radiation-induced NF-kappaB activation via inhibition of radiation-induced phosphorylation and degradation of inhibitor of kappaB alpha, inhibition of inhibitor of kappaB kinase activity, and inhibition of Akt phosphorylation. Curcumin also suppressed NF-kappaB-regulated gene products (Bcl-2, Bcl-x(L), inhibitor of apoptosis protein-2, cyclooxygenase-2, and cyclin D1).

Conclusions: Our results suggest that transient inducible NF-kappaB activation provides a prosurvival response to radiation that may account for development of radioresistance. Curcumin blocks this signaling pathway and potentiates the antitumor effects of radiation therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / radiotherapy
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / radiotherapy*
  • Curcumin / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation / drug effects
  • HT29 Cells
  • Humans
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • NF-kappa B / radiation effects
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / metabolism
  • Neoplasm Proteins / radiation effects
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • Radiation Tolerance / physiology*
  • Radiation-Sensitizing Agents / pharmacology*
  • Rectal Neoplasms / metabolism
  • Rectal Neoplasms / radiotherapy


  • Enzyme Inhibitors
  • NF-kappa B
  • Neoplasm Proteins
  • Radiation-Sensitizing Agents
  • Proto-Oncogene Proteins c-akt
  • Curcumin