An indolylquinoline derivative activates DNA damage response and apoptosis in human hepatocellular carcinoma cells

Chun Yen Liu, Chang Hung Hsieh, Seung Hun Kim, Jing Ping Wang, Yu Lin Ni, Chun Li Su, Ching Fa Yao, Kang Fang

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Human liver cancer is one of the most frequently diagnosed cancers worldwide. The development of resistance to therapy limits the application against the disease. To improve treatment, new effective anticancer agents are constantly pursued. Previously, we reported that an indolylquinoline, 3-((7-ethyl-1H-indol-3-yl)-methyl)-2-methylquinoline (EMMQ), is effective in suppressing the growth of human lung cancer by impairing mitochondria functions. The present study revealed that EMMQ inhibited cell growth and induced apoptosis in liver cancer cells, but not in normal cells. This study demonstrated that EMMQ induced DNA damage by activating p53 and H2AX and cell arrest by suppressing cyclin D1 and CDK2. Damaged DNA injured mitochondrial functions by lowering the membrane potential and producing reactive oxygen species. The subsequent mitochondrial cytochrome c release attenuated pro-survival signals and increased apoptotic characteristics. Introduction of p53 shRNA abrogated drug effects by reducing DNA damage while maintaining mitochondria integrity. In brief, the study demonstrates that the effectiveness of EMMQ accentuated apoptosis of hepatocarcinoma cells by activating p53. Based on these collective findings, the study offered a new perspective of EMMQ that was shown to be a promising candidate to treat liver cancer.

Original languageEnglish
Pages (from-to)2431-2441
Number of pages11
JournalInternational Journal of Oncology
Volume49
Issue number6
DOIs
Publication statusPublished - 2016 Dec

Keywords

  • Apoptosis
  • Human liver cancer cells
  • Indolylquinoline

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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