Abundance of aryl hydrocarbon receptor potentiates benzo[a]pyrene-induced apoptosis in Hepa1c1c7 cells via CYP1A1 activation

Jin Yong Chung, Ji Young Kim, Won Rok Kim, Seung Gee Lee, Yoon Jae Kim, Ji Eun Park, Yeon Pyo Hong, Young Jin Chun, Young Chul Park, Seunghoon Oh, Ki Soo Yoo, Young Hyun Yoo, Jong Min Kim

Research output: Contribution to journalArticle

Abstract

Although B[a]P-induced apoptosis has been demonstrated in Hepa1c1c7 cells, the cellular signaling pathway(s) by which benzo[a]pyrene (B[a]P) elicits a cytotoxicity-mediated apoptogenic role remains to be elucidated. In this study, we showed that B[a]P induces apoptosis in a p53-mediated and caspase-3-dependent manner, which relates to the accumulation of the S phase of the cell cycle. Importantly, we have shown for the first time that Hepa1c1c7 cells retain a considerably high content of aryl hydrocarbon receptor (AhR) protein before B[a]P exposure, assuming that this status enables the cells to respond to B[a]P more readily as well as more efficiently. B[a]P treatment resulted in the downregulation of AhR and induced cytochrome P450 1A1 (CYP1A1) (but not cytochrome P450 1B1 (CYP1B1)) expression and activity. While α-naphtoflavone (α-NF) and ellipticine suppressed B[a]P-induced CYP1A1 activation as well as apoptosis, the 2,3′,4,5′-tetramethoxystilbene (TMS) and pyrene, known CYP1B1 inhibitors, failed to inhibit apoptosis. However, α-NF alone significantly increased CYP1A1 protein expression but not its activity, suggesting that α-NF more likely works as an AhR agonist in Hepa1c1c7 cells after B[a]P, rather than a direct inhibitor of CYP1A1 activity. In conclusion, it is suggested that the abundance of endogenous AhR level is an indispensable condition for an efficient cellular signaling of B[a]P and that control of AhR activity in Hepa1c1c7 cells might be important to cell fate resulting from CYP1A1 activation after B[a]P.

Original languageEnglish (US)
Pages (from-to)62-72
Number of pages11
JournalToxicology
Volume235
Issue number1-2
DOIs
StatePublished - Jun 3 2007
Externally publishedYes

Keywords

  • AhR
  • Apoptosis
  • Benzo[a]pyrene
  • CYP1A1
  • CYP1B1
  • Hepatoma cells

ASJC Scopus subject areas

  • Toxicology

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  • Cite this

    Chung, J. Y., Kim, J. Y., Kim, W. R., Lee, S. G., Kim, Y. J., Park, J. E., Hong, Y. P., Chun, Y. J., Park, Y. C., Oh, S., Yoo, K. S., Yoo, Y. H., & Kim, J. M. (2007). Abundance of aryl hydrocarbon receptor potentiates benzo[a]pyrene-induced apoptosis in Hepa1c1c7 cells via CYP1A1 activation. Toxicology, 235(1-2), 62-72. https://doi.org/10.1016/j.tox.2007.03.013