Effects of anthocyanins on the AhR-CYP1A1 signaling pathway in human hepatocytes and human cancer cell lines

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

Research output: Contribution to journalArticle

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Abstract

Anthocyanins are plant pigments occurring in flowers and berry fruits. Since a phenomenon of food-drug interactions is increasingly emerging, we examined the effects of 21 major anthocyanins and the extracts from 3 food supplements containing anthocyanins on the aryl hydrocarbon receptor (AhR)-cytochrome P450 CYP1A1 signaling pathway in human hepatocytes and human hepatic HepG2 and intestinal LS174T cancer cells. Pelargonidin-3-. O-rutinoside (PEL-2) and cyanidin-3,5-. O-diglucoside (CYA-3) dose-dependently activated AhR, as revealed by gene reporter assay. PEL-2 and CYA-3 induced CYP1A1 mRNA but not protein in HepG2 and LS174T cells. Neither compounds induced CYP1A1 mRNA and protein in four different primary human hepatocytes cultures. The effects of PEL-2 and CYA-3 on AhR occurred by ligand-dependent and ligand-independent mechanisms, respectively, as demonstrated by ligand binding assay. In a direct enzyme inhibition assay, none of the antocyanins tested inhibited the CYP1A1 marker activity to less than 50% even at 100. μM concentration. PEL-2 and CYA-3 at 100. μM inhibited CYP1A1 to 79% and 65%, respectively. In conclusion, with exception of PEL-2 and CYA-3, there were no effects of 19 major anthocyanins and 3 food supplements containing anthocyanins on AhR-CYP1A1 signaling, implying zero potential of these compounds for food-drug interactions with respect to AhR-CYP1A1 pathway.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalToxicology Letters
Volume221
Issue number1
DOIs
StatePublished - Jul 1 2013

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Aryl Hydrocarbon Receptors
Cytochrome P-450 CYP1A1
Anthocyanins
Hepatocytes
Cells
Cell Line
Neoplasms
Drug interactions
Food-Drug Interactions
Assays
Dietary Supplements
Ligands
Fruit
Intestinal Neoplasms
Enzyme inhibition
Messenger RNA
Hep G2 Cells
Enzyme Assays
Fruits
Reporter Genes

Keywords

  • AhR
  • Anthocyanins
  • Aryl hydrocarbon receptor
  • Cytochrome P450
  • Food supplements
  • Food-drug interactions
  • TCDD

ASJC Scopus subject areas

  • Toxicology

Cite this

Kamenickova, A., Anzenbacherova, E., Pavek, P., Soshilov, A. A., Denison, M. S., Zapletalova, M., ... Dvorak, Z. (2013). Effects of anthocyanins on the AhR-CYP1A1 signaling pathway in human hepatocytes and human cancer cell lines. Toxicology Letters, 221(1), 1-8. https://doi.org/10.1016/j.toxlet.2013.05.007

Effects of anthocyanins on the AhR-CYP1A1 signaling pathway in human hepatocytes and human cancer cell lines. / Kamenickova, Alzbeta; Anzenbacherova, Eva; Pavek, Petr; Soshilov, Anatoly A.; Denison, Michael S.; Zapletalova, Michaela; Anzenbacher, Pavel; Dvorak, Zdenek.

In: Toxicology Letters, Vol. 221, No. 1, 01.07.2013, p. 1-8.

Research output: Contribution to journalArticle

Kamenickova, A, Anzenbacherova, E, Pavek, P, Soshilov, AA, Denison, MS, Zapletalova, M, Anzenbacher, P & Dvorak, Z 2013, 'Effects of anthocyanins on the AhR-CYP1A1 signaling pathway in human hepatocytes and human cancer cell lines', Toxicology Letters, vol. 221, no. 1, pp. 1-8. https://doi.org/10.1016/j.toxlet.2013.05.007
Kamenickova A, Anzenbacherova E, Pavek P, Soshilov AA, Denison MS, Zapletalova M et al. Effects of anthocyanins on the AhR-CYP1A1 signaling pathway in human hepatocytes and human cancer cell lines. Toxicology Letters. 2013 Jul 1;221(1):1-8. https://doi.org/10.1016/j.toxlet.2013.05.007
Kamenickova, Alzbeta ; Anzenbacherova, Eva ; Pavek, Petr ; Soshilov, Anatoly A. ; Denison, Michael S. ; Zapletalova, Michaela ; Anzenbacher, Pavel ; Dvorak, Zdenek. / Effects of anthocyanins on the AhR-CYP1A1 signaling pathway in human hepatocytes and human cancer cell lines. In: Toxicology Letters. 2013 ; Vol. 221, No. 1. pp. 1-8.
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abstract = "Anthocyanins are plant pigments occurring in flowers and berry fruits. Since a phenomenon of food-drug interactions is increasingly emerging, we examined the effects of 21 major anthocyanins and the extracts from 3 food supplements containing anthocyanins on the aryl hydrocarbon receptor (AhR)-cytochrome P450 CYP1A1 signaling pathway in human hepatocytes and human hepatic HepG2 and intestinal LS174T cancer cells. Pelargonidin-3-. O-rutinoside (PEL-2) and cyanidin-3,5-. O-diglucoside (CYA-3) dose-dependently activated AhR, as revealed by gene reporter assay. PEL-2 and CYA-3 induced CYP1A1 mRNA but not protein in HepG2 and LS174T cells. Neither compounds induced CYP1A1 mRNA and protein in four different primary human hepatocytes cultures. The effects of PEL-2 and CYA-3 on AhR occurred by ligand-dependent and ligand-independent mechanisms, respectively, as demonstrated by ligand binding assay. In a direct enzyme inhibition assay, none of the antocyanins tested inhibited the CYP1A1 marker activity to less than 50{\%} even at 100. μM concentration. PEL-2 and CYA-3 at 100. μM inhibited CYP1A1 to 79{\%} and 65{\%}, respectively. In conclusion, with exception of PEL-2 and CYA-3, there were no effects of 19 major anthocyanins and 3 food supplements containing anthocyanins on AhR-CYP1A1 signaling, implying zero potential of these compounds for food-drug interactions with respect to AhR-CYP1A1 pathway.",
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