HSp90 inhibitors, geldanamycin and radicicol, enhance fisetin-induced cytotoxicity via induction of apoptosis in human colonic cancer cells

研究成果: 雜誌貢獻文章

12 引文 斯高帕斯(Scopus)

摘要

We revealed the cytotoxic effect of the flavonoid, fisetin (FIS), on human COLO205 colon cancer cells in the presence and absence of the HSP90 inhibitors, geldanamycin (GA) and radicicol (RAD). Compared to FIS treatment alone of COLO205 cells, GA and RAD significantly enhanced FIS-induced cytotoxicity, increased expression of cleaved caspase-3 and the PAPR protein, and produced a greater density of DNA ladder formation. GA and RAD also reduced the MMPs with induction of caspase-9 protein cleavage in FIS-treated COLO205 cells. Increased caspase-3 and -9 activities were detected in COLO205 cells treated with FIS+GA or FIS+RAD, and the intensity of DNA ladder formation induced by FIS+GA was reduced by adding the caspase-3 inhibitor, DEVD-FMK. A decrease in Bcl-2 but not Bcl-XL or Bax protein by FIS+GA or FIS+RAD was identified in COLO205 cells by Western blotting. A reduction in p53 protein with increased ubiquitin-tagged proteins was observed in COLO205 cells treated with FIS+GA or FIS+RAD. Furthermore, GA and RAD reduced the stability of the p53 protein in COLO205 cells under FIS stimulation. The evidence supports HSP90 inhibitors possibly sensitizing human colon cancer cells to FIS-induced apoptosis, and treating colon cancer by combining HSP90 inhibitors with FIS deserves further in vivo study.
原文英語
文章編號987612
期刊Evidence-based Complementary and Alternative Medicine
2013
DOIs
出版狀態已發佈 - 2013

ASJC Scopus subject areas

  • Complementary and alternative medicine

指紋 深入研究「HSp90 inhibitors, geldanamycin and radicicol, enhance fisetin-induced cytotoxicity via induction of apoptosis in human colonic cancer cells」主題。共同形成了獨特的指紋。

  • 引用此