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6‐Formylindolo[3,2‐b]carbazole reduces apoptosis induced by benzo[a]pyrene in a mitochondrial‐dependent manner
Author(s) -
Gan Min,
Ding Hongbiao,
Chen Gang
Publication year - 2020
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.11450
Subject(s) - chemistry , aryl hydrocarbon receptor , apoptosis , benzo(a)pyrene , cell growth , biochemistry , carcinogen , microbiology and biotechnology , biology , transcription factor , gene
Benzo[a]pyrene (B[a]P), a potent carcinogen, has been proved that it can induce apoptosis via activation of the aryl hydrocarbon receptor (AhR) pathway. The metabolite of tryptophan 6‐formylindolo[3,2‐b]carbazole (FICZ), an endogenous activator of AhR, plays bifunctional roles in cell growth and apoptosis. However, whether and how FICZ can reduce the toxicity of B[a]P and the mechanism underlying this remain unclear. In this study, FICZ interfered with the toxicity of B[a]P in mouse hepatocarcinoma cell line Hepa1‐6. The results of the MTT assay indicated that FICZ and B[a]P made opposite effects on cell proliferation. The scratch‐wound healing assay showed that B[a]P (1 µM for 24 hr) exposure triggered cell migration and that was inhibited by FICZ (10 nM). In addition, FICZ ameliorated B[a]P‐induced apoptosis by inhibiting reactive oxygen species generation and caspase‐3 activation, as well as increasing reduced glutathione level in mitochondria. Furthermore, gene expression analyses indicated that FICZ competed with B[a]P, which reduced the transcriptional activation of the cyp1a1 and cyp1b1 genes, as well as Bcl2 and P53 . Accordingly, the interaction between FICZ and B[a]P in the AhR pathway inhibited apoptosis in a mitochondrial‐dependent manner, suggesting that endogenous compound may reduce the toxicity of exogenous pollutant in vivo and providing an available way to improve health condition related to the hepatic metabolic disorder.