An indolylquinoline derivative promotes apoptosis in human lung cancer cells by impairing mitochondrial functions.
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.
Department of Life Science, National Taiwan Normal University, 88 Ting-Chow Rd, Sec 4, Taipei, 116, Taiwan.
Chun-Yen
CY
Liu
Department of Life Science, National Taiwan Normal University, 88 Ting-Chow Rd, Sec 4, Taipei, 116, Taiwan.
Pei-Tsen
PT
Wu
Department of Life Science, National Taiwan Normal University, 88 Ting-Chow Rd, Sec 4, Taipei, 116, Taiwan.
Jing-Ping
JP
Wang
Department of Life Science, National Taiwan Normal University, 88 Ting-Chow Rd, Sec 4, Taipei, 116, Taiwan.
Po-Wei
PW
Fan
Department of Life Science, National Taiwan Normal University, 88 Ting-Chow Rd, Sec 4, Taipei, 116, Taiwan.
Chang-Hung
CH
Hsieh
Department of Human Development and Family Studies, National Taiwan Normal University, Taipei, Taiwan.
Chun-Li
CL
Su
Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chien-Chih
CC
Chiu
Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan.
Ching-Fa
CF
Yao
Department of Life Science, National Taiwan Normal University, 88 Ting-Chow Rd, Sec 4, Taipei, 116, Taiwan. kangfang@ntnu.edu.tw.
Kang
K
Fang
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
C000617120:3-((7-ethyl-1H-indol-3-yl)-methyl)-2-methylquinoline; D000970:Antineoplastic Agents; D007211:Indoles; D011804:Quinolines; D016159:Tumor Suppressor Protein p53; C030374:indole; D045304:Cytochromes c; C037219:quinoline; D053148:Caspase 3
Apoptosis; Human non-small-cell-lung-cancer cells; Indolylquinoline; RNA interference; p53