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

Apoptosis : an International Journal on Programmed Cell Death
Chun-Yen LiuKang Fang

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...Continue Reading

References

Sep 1, 1996·The Journal of Experimental Medicine·P MarchettiG Kroemer
Jan 5, 2000·Oncogene·N D Lakin, S P Jackson
Feb 24, 2001·Annals of the New York Academy of Sciences·A SaleemE H Rubin
Sep 16, 2003·Journal of Cell Science·Susan HauptYgal Haupt
Jun 7, 2005·Cell·Douglas R Green
Sep 2, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Marcello TiseoAndrea Ardizzoni
Aug 11, 2006·Trends in Molecular Medicine·Wynand P Roos, Bernd Kaina
Nov 28, 2006·Nature Reviews. Cancer·Franck Toledo, Geoffrey M Wahl
Jun 2, 2007·The Lancet Oncology·Christophe MarietteJean-Pierre Triboulet
Jun 15, 2007·Toxicologic Pathology·Susan Elmore
Dec 8, 2007·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Einat SouliShmuel Yannai
Mar 4, 2008·Trends in Cell Biology·Jerry E Chipuk, Douglas R Green
Oct 19, 2010·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Alex Chang
Nov 10, 2010·Journal of Experimental & Clinical Cancer Research : CR·Cheng ChangJun Luo
Apr 28, 2011·The EMBO Journal·Tom J PettyThanos D Halazonetis
May 17, 2013·Apoptosis : an International Journal on Programmed Cell Death·Ying Ding, Thu Annelise Nguyen
Aug 21, 2013·Toxicology and Applied Pharmacology·Jing-Ping WangKang Fang
Sep 7, 2013·Cell Death & Disease·P BoseK Riabowol
Nov 19, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Madeeha AqilJames A Radosevich
Jul 31, 2014·European Journal of Medicinal Chemistry·Obaid AfzalSandhya Bawa
Mar 12, 2015·Cancer Cell·Elodie Pronier, Ross L Levine

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Citations

Feb 14, 2016·Expert Opinion on Therapeutic Targets·Ruth NussinovOzlem Keskin
Dec 24, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wen-Chang ChenChing-Fa Yao
Jun 22, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Martyna KorczAnita Kornicka
Jul 26, 2017·Apoptosis : an International Journal on Programmed Cell Death·Yu-Ling NiKang Fang
Dec 1, 2017·Apoptosis : an International Journal on Programmed Cell Death·Chang-Heng HsiehKang Fang
Apr 5, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jyothi Dhuguru, Rachid Skouta

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