Curcumin modulates the radiosensitivity of colorectal cancer cells by suppressing constitutive and inducible NF-kappaB activity.
Curcumin modulates the radiosensitivity of colorectal cancer cells by suppressing constitutive and inducible NF-kappaB activity.
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DOI：
10.1016/j.ijrobp.2009.06.034
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发表时间：
2009-10-01
影响因子：
7
通讯作者：
Krishnan, Suin
中科院分区：
文献类型：
--
作者：
Sandur, Santosh K.;Deorukhkar, Amit;Pandey, Manoj K.;Pabon, Ana Maria;Shentu, Shujun;Guha, Sushovan;Aggarwal, Bharat B.;Krishnan, Suin
Radiation therapy is an integral part of the preoperative treatment of rectal cancers. However, only a minority of patients achieve a complete pathological response to therapy due to 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. Human colorectal cancer cells were exposed to clinically relevant doses of gamma rays and the mechanism of their radioresistance was investigated. We characterize the transcription factor nuclear factor-κB (NF-κB) activation as a mechanism of inducible radioresistance in colorectal cancer and use curcumin, the active ingredient in the yellow spice turmeric to overcome this resistance. Curcumin inhibited the proliferation and the post-irradiation clonogenic survival of multiple colorectal cancer cell lines. Radiation stimulated NF-κB activity in a dose- and time-dependent manner while curcumin suppressed this radiation-induced NF-κB activation via inhibition of radiation-induced phosphorylation and degradation of IκBα, inhibition of IKK activity, and inhibition of Akt phosphorylation. Curcumin also suppressed NF-κB regulated gene products (Bcl-2, Bcl-xL, inhibitor of apoptosis protein-2, cyclooxygenase-2, and cyclin D1). Our results suggest that transient inducible NF-κB activation provides a pro-survival response to radiation that may account for development of radioresistance. Curcumin blocks this signaling pathway and potentiates the anti-tumor effects of radiation therapy.
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影响因子：
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通讯作者：
Aggarwal, BB
影响因子：
45.3
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Mohiuddin, M;Winter, K;Willett, C
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Willett, C
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20.3
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通讯作者：
Aggarwal, BB
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作者：
Lao, Christopher D;Ruffin, Mack T 4th;Brenner, Dean E
通讯作者：
Brenner, Dean E