curcumin greatly increases efficacy of radiation against colon cancer

curcumin greatly increases efficacy of radiation against colon cancer

* w w w .ncbi.nlm.nih.gov/pubmed/18381954?ordinalpos=1&itool=EntrezSystem2
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Clin Cancer Res. 2008 Apr 1;14(7):2128-36.

Curcumin Sensitizes Human Colorectal Cancer Xenografts in Nude Mice to
{gamma}-Radiation by Targeting Nuclear Factor-{kappa}B-Regulated Gene
Products.

Kunnumakkara AB, Diagaradjane P, Guha S, Deorukhkar A, Shentu S, Aggarwal
BB, Krishnan S.
Authors' Affiliations: Departments of Experimental Therapeutics, Radiation
Oncology, and Gastroenterology, Hepatology and Nutrition, The University of
Texas M. D. Anderson Cancer Center, Houston, Texas.

PURPOSE: How colorectal cancer develops resistance to gamma-radiation is not
fully understood, but the transcription factor nuclear factor-kappaB
(NF-kappaB) and NF-kappaB-regulated gene products have been proposed as
mediators. Because curcumin, a component of turmeric (Curcuma longa), has
been shown to suppress NF-kappaB activation, whether it can sensitize the
colorectal cancer to gamma-radiation was investigated in colorectal cancer
xenografts in nude mice. EXPERIMENTAL DESIGN: We established HCT 116
xenograft in nude mice, randomized into four groups, and treated with
vehicle (corn oil), curcumin, gamma-radiation, and curcumin in combination
with gamma-radiation. NF-kappaB modulation was ascertained using
electrophoretic mobility shift assay and immunohistochemistry. Markers of
proliferation, angiogenesis, and invasion were monitored by
immunohistochemistry and Western blot analysis. RESULTS: Curcumin
significantly enhanced the efficacy of fractionated radiation therapy by
prolonging the time to tumor regrowth (P = 0.02) and by reducing the Ki-67
proliferation index (P < 0. 001). Moreover, curcumin suppressed NF-kappaB
activity and the expression of NF-kappaB-regulated gene products (cyclin D1,
c-myc, Bcl-2, Bcl-xL, cellular inhibitor of apoptosis protein-1,
cyclooxygenase-2, matrix metalloproteinase-9, and vascular endothelial
growth factor), many of which were induced by radiation therapy and mediate
radioresistance. The combination of curcumin and radiation therapy also
suppressed angiogenesis, as indicated by a decrease in vascular endothelial
growth factor and microvessel density (P = 0.002 versus radiation alone).
CONCLUSION: Collectively, our results suggest that curcumin potentiates the
antitumor effects of radiation therapy in colorectal cancer by suppressing
NF-kappaB and NF-kappaB-regulated gene products, leading to inhibition of
proliferation and angiogenesis.