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

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)447-457
Number of pages11
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume378
Issue number5
DOIs
Publication statusPublished - Nov 2008
Externally publishedYes

Keywords

  • AIF
  • Anticancer
  • Caspase-independent
  • Denbinobin
  • DNA damage

ASJC Scopus subject areas

  • Pharmacology

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