Denbinobin induces apoptosis by apoptosis-inducing factor releasing and DNA damage in human colorectal cancer HCT-116 cells

Tzu Hsuan Chen, Shiow Lin Pan, Jih Hwa Guh, Chien Chih Chen, Yao Ting Huang, Hui Chen Pai, Che Ming Teng

研究成果: 雜誌貢獻文章

16 引文 斯高帕斯(Scopus)

摘要

Denbinobin is a phenanthraquinone derivative present in the stems of Ephemerantha lonchophylla. We showed that denbinobin induces apoptosis in human colorectal cancer cells (HCT-116) in a concentration-dependent manner. The addition of a pan-caspase inhibitor (zVAD-fmk) did not suppress the denbinobin-induced apoptotic effect, and denbinobin-induced apoptosis was not accompanied by processing of procaspase-3, -6, -7, -9, and -8. However, denbinobin triggered the translocation of the apoptosis-inducing factor (AIF) from the mitochondria into the nucleus. Small interfering RNA targeting of AIF effectively protected HCT-116 cells against denbinobin-induced apoptosis. Denbinobin treatment also caused DNA damage, activation of the p53 tumor suppressor gene, and upregulation of numerous downstream effectors (p21 WAF1/CIP1, Bax, PUMA, and NOXA). A HCT-116 xenograft model demonstrated the in vivo efficacy and low toxicity of denbinobin. Taken together, our findings suggest that denbinobin induces apoptosis of human colorectal cancer HCT-116 cells via DNA damage and an AIF-mediated pathway. These results indicate that denbinobin has potential as a novel anticancer agent.
原文英語
頁(從 - 到)447-457
頁數11
期刊Naunyn-Schmiedeberg's Archives of Pharmacology
378
發行號5
DOIs
出版狀態已發佈 - 十一月 2008
對外發佈Yes

ASJC Scopus subject areas

  • Pharmacology

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