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Effect of Radiation on Human Intestinal Microvascular Endothelial Cells (HIMEC): Role of Akt/mTOR and NFκB
Author(s) -
Rafiee Parvaneh,
Binion David G,
Wellner Michael,
Otterson Mary F
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.750.8
Subject(s) - curcumin , pi3k/akt/mtor pathway , protein kinase b , cancer research , angiogenesis , apoptosis , chemistry , nf κb , signal transduction , phosphorylation , ly294002 , medicine , microbiology and biotechnology , pharmacology , biology , biochemistry
Radiation therapy is an essential modality in the treatment of colorectal cancers. Radiation exerts an anti‐angiogenic effect on tumors, inhibiting endothelial proliferation and survival in the tumor microvasculature. However, damage from low levels of irradiation can induce a paradoxical effect, stimulating survival in endothelial cells. We used HIMEC to define effects of low level radiation on these gut specific endothelial cells. 2 Gy of irradiation activates NFκB and the PI3K/Akt pathway, which is involved in cell cycle re‐entry and cell survival in HIMEC. A downstream target of PI3K/Akt is mammalian target of rapamycin (mTOR), which contributes to cell proliferation and angiogenesis. The aim of this study was to investigate the signaling molecules involved in the radio‐sensitizing effects of curcumin on HIMEC subjected to low level of irradiation. We have demonstrated that exposure of HIMEC to low level of irradiation induced mTOR and Akt phosphorylation, which was attenuated by curcumin, rapamycin and LY294002. Activation of NFκB by low level of irradiation was inhibited by curcumin and SN‐50. Curcumin also induced apoptosis by induction of caspase‐3 cleavage in irradiated HIMEC. In conclusion, curcumin significantly inhibited NFκB and attenuated the effect of irradiation‐induced pro‐survival signaling through the PI3k/Akt/mTOR and NFκB pathways in these gut specific endothelial cells. Curcumin may be a potential radio‐sensitizing agent for enhanced anti‐angiogenic effect in colorectal cancer radiation therapy.