Pelargonidin activates the AhR and induces CYP1A1 in primary human hepatocytes and human cancer cell lines HepG2 and LS174T

Alzbeta Kamenickova, Eva Anzenbacherova, Petr Pavek, Anatoly A. Soshilov, Michael S. Denison, Pavel Anzenbacher, Zdenek Dvorak

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34 Scopus citations

Abstract

We examined the effects of anthocyanidins (cyanidin, delphinidin, malvidin, peonidin, petunidin, pelargonidin) on the aryl hydrocarbon receptor (AhR)-CYP1A1 signaling pathway in human hepatocytes, hepatic HepG2 and intestinal LS174T cancer cells. AhR-dependent reporter gene expression in transfected HepG2 cells was increased by pelargonidin in a concentration-dependent manner at 24. h. Similarly, pelargonidin induced the expression of CYP1A1 mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5. nM 2,3,7,8-tetrachlorodibenzodioxin (TCDD), the most potent activator of AhR. CYP1A1 and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme. Ligand binding analysis demonstrated that pelargonidin was a weak ligand of AhR.Enzyme kinetic analyses using human liver microsomes revealed inhibition of CYP1A1 activity by delphinidin (IC50 78μM) and pelargonidin (IC50 33μM).Overall, although most anthocyanidins had no effects on AhR-CYP1A1 signaling, pelargonidin can bind to and activate the AhR and AhR-dependent gene expression, and pelargonidin and delphinidin inhibit the CYP1A1 catalytic activity.

Original languageEnglish (US)
Pages (from-to)253-259
Number of pages7
JournalToxicology Letters
Volume218
Issue number3
DOIs
StatePublished - Apr 6 2013

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Keywords

  • Anthocyanidins
  • Aryl hydrocarbon receptor
  • Cytochrome P450
  • Food-drug interactions
  • Pelargonidin

ASJC Scopus subject areas

  • Toxicology

Cite this

Kamenickova, A., Anzenbacherova, E., Pavek, P., Soshilov, A. A., Denison, M. S., Anzenbacher, P., & Dvorak, Z. (2013). Pelargonidin activates the AhR and induces CYP1A1 in primary human hepatocytes and human cancer cell lines HepG2 and LS174T. Toxicology Letters, 218(3), 253-259. https://doi.org/10.1016/j.toxlet.2013.01.020