An indolylquinoline derivative promotes apoptosis in human lung cancer cells by impairing mitochondrial functions

Chun Yen Liu, Pei Tsen Wu, Jing Ping Wang, Po Wei Fan, Chang Hung Hsieh, Chun Li Su, Chien Chih Chiu, Ching Fa Yao, Kang Fang

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

A number of effective anti-cancer drugs contain either indole or quinoline group. Compounds fused indole and quinoline moieties altogether as indolylquinoline were rarely reported as anti-cancer agents. We reported here that a synthetic indolylquinoline derivative, 3-((7-ethyl-1H-indol-3-yl)-methyl)-2-methylquinoline (EMMQ), inhibited the growth of human non-small cell lung cancer (NSCLC) cells in dose- and time-dependent manners. The cytotoxicity was mediated through apoptotic cell death that began with mitochondrial membrane potential interruption and DNA damage. EMMQ caused transient elevation of p53 that assists in cytochrome c release, cleavage of downstream PARP and procaspase-3 and mitochondria-related apoptosis. The degree of apoptotic cell death depends on the status of tumor suppressor p53 of the target cells. H1299 cells with stable ectopic expression of p53 induced cytotoxicity by disrupting mitochondria functions that differed with those transfected with mutant p53. Knocking-down of p53 attenuated drug effects. EMMQ suppressed the growth of A549 tumor cells in xenograft tumors by exhibiting apoptosis characteristics. Given its small molecular weight acting as an effective p53 regulator in NSCLC cells, EMMQ could be an addition to the current list of lung cancer treatment.

Original languageEnglish
Pages (from-to)1471-1482
Number of pages12
JournalApoptosis
Volume20
Issue number11
DOIs
Publication statusPublished - 2015 Nov 30

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Keywords

  • Apoptosis
  • Human non-small-cell-lung-cancer cells
  • Indolylquinoline
  • RNA interference
  • p53

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

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