C086, a novel analog of curcumin, induces growth inhibition and downregulation of NFκB in colon cancer cells and xenograft tumors
C086, a novel analog of curcumin, induces growth inhibition and downregulation of NFκB in colon cancer cells and xenograft tumors
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DOI：
10.4161/cbt.12.9.17671
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发表时间：
2011-11-01
影响因子：
3.6
通讯作者：
Xu, Jianhua
中科院分区：
文献类型：
--
作者：
Chen, Chun;Liu, Yang;Xu, Jianhua
New analogs of curcumin with improved properties are needed to meet therapeutic requirements. In this study, the effects of C086 on growth inhibition and NF kappa B pathway regulation were investigated in colon cancer cells and xenograft tumors. C086 exhibited potent antiproliferative activity in all six colon cancer cell lines. In a xenograft model of SW480 cells in nude mice, the oral administration of C086 showed significant growth suppression of SW480 tumors, and both protein gel blot and immunohistochemistry analyses showed decreased NF kappa B (p65) expression in tumor tissues. Using TNF alpha to induce NF kappa B activation in SW480 cells, it was revealed that C086 inhibited I kappa B alpha phosphorylation and its subsequent degradation, and suppressed the nuclear translocation and DNA binding activity of NF kappa B. C-Myc, cyclin D1 and Bcl-2, NF kappa B-regulated gene products involving in cellular proliferation and antiapoptosis, were decreased in the C086 treated groups. This effect was accompanied by pro-apoptosis of C086 in colon cancer cells and lower expression of PCNA in C086 treated colon cancer xenografts. Immunostaining for CD31 showed that there were fewer microvessels in C086 treated SW480 tumors and NF kappa B-targeted gene products involved in angiogenesis (i.e., vascular endothelial growth factor, matrix metalloproteinase-9) were also downregulated. C086 also inhibited bovine aortic endothelial cell (BAEC) proliferation and tube formation in Matrigel. Overall, our results suggest that C086 is a potent antitumor agent and has promising future in colon cancer. C086 suppressed NF kappa B activation through inhibition of I kappa Ba phosphorylation. Downregulation of NF kappa B-regulated gene products contributed to the antiproliferation, pro-apoptosis and antiangiogenesis effect of C086.
