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Curcumin modulates the radiosensitivity of colorectal cancer cells by suppressing constitutive and inducible NF-kappaB activity.
- Source :
-
International journal of radiation oncology, biology, physics [Int J Radiat Oncol Biol Phys] 2009 Oct 01; Vol. 75 (2), pp. 534-42. - Publication Year :
- 2009
-
Abstract
- 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.<br />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.<br />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).<br />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.
- Subjects :
- Apoptosis
Cell Line, Tumor
Cell Proliferation drug effects
Colonic Neoplasms metabolism
Colonic Neoplasms radiotherapy
Colorectal Neoplasms metabolism
Dose-Response Relationship, Drug
Enzyme Inhibitors pharmacology
Gene Expression Regulation drug effects
HT29 Cells
Humans
NF-kappa B metabolism
NF-kappa B radiation effects
Neoplasm Proteins metabolism
Neoplasm Proteins radiation effects
Phosphorylation
Proto-Oncogene Proteins c-akt antagonists & inhibitors
Proto-Oncogene Proteins c-akt metabolism
Rectal Neoplasms metabolism
Rectal Neoplasms radiotherapy
Colorectal Neoplasms radiotherapy
Curcumin pharmacology
NF-kappa B antagonists & inhibitors
Neoplasm Proteins antagonists & inhibitors
Radiation Tolerance physiology
Radiation-Sensitizing Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-355X
- Volume :
- 75
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- International journal of radiation oncology, biology, physics
- Publication Type :
- Academic Journal
- Accession number :
- 19735878
- Full Text :
- https://doi.org/10.1016/j.ijrobp.2009.06.034