Curcumin analog, GO-Y078, overcomes resistance to tumor angiogenesis inhibitors

Cancer Science
Kazuhiro ShimazuHiroyuki Shibata

Abstract

Tumor angiogenesis inhibition is one of the most potent strategies in cancer chemotherapy. From past clinical studies, inhibition of the vascular endothelial growth factor pathway successfully treats malignant tumors. However, vascular endothelial growth factor inhibitors alone cannot cure tumors. Moreover, resistance to small molecule inhibitors has also been reported. Herein, we show the antiangiogenic potential of a newly synthesized curcumin analog, GO-Y078, that possibly functions through inhibition of actin stress fiber formation, resulting in mobility inhibition; this mechanism is different from that of vascular endothelial growth factor inhibition. In addition, we examined the detailed mechanism of action of the antiangiogenesis potential of GO-Y078 using human umbilical venous epithelial cells resistant to angiogenesis inhibitors (HUVEC-R). GO-Y078 inhibited the growth and mobility of HUVEC-R at 0.75 μmol/L concentration. Expression analyses by microarray and RT-PCR showed that expressions of genes including that of fibronectin 1 were significantly suppressed. Among these genes, fibronectin 1 is abundantly expressed and, therefore, seems to be a good target for GO-Y078. In a knockdown experiment using Si-oligo of fibro...Continue Reading

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Citations

Feb 19, 2020·Anti-cancer Agents in Medicinal Chemistry·Nayane de SouzaSilvya S Maria-Engler

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Methods Mentioned

BETA
PCR
ELISA
transfection

Software Mentioned

CodeLink
Stat Mate III
CodeLink Expression Analysis

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