Caffeic acid phenethyl ester inhibits 3-MC-induced CYP1A1 expression through induction of hypoxia-inducible factor-1α

Biochem Biophys Res Commun. 2015 Sep 25;465(3):562-8. doi: 10.1016/j.bbrc.2015.08.060. Epub 2015 Aug 18.

Abstract

Caffeic acid phenethyl ester (CAPE), a natural component of propolis, is reported to have anticarcinogenic properties, although its precise chemopreventive mechanism remains unclear. In this study, we examined the effects of CAPE on 3-methylcholanthrene (3-MC)-induced CYP1A1 expression and activities. CAPE reduced the formation of the benzo[a]pyrene-DNA adduct. Moreover, CAPE inhibited 3-MC-induced CYP1A1 activity, mRNA expression, protein level, and promoter activity. CAPE treatment also decreased 3-MC-inducible xenobiotic-response element (XRE)-linked luciferase, aryl hydrocarbons receptor (AhR) transactivation and nuclear localization. CAPE induced hypoxia inducible factor-1α (HIF-1α) protein level and HIF-1α responsible element (HRE) transcriptional activity. CAPE-mediated HIF-1α reduced 3-MC-inducible CYP1A1 protein expression. Taken together, CAPE decreases 3-MC-mediated CYP1A1 expression, and this inhibitory response is associated with inhibition of AhR and HIF-1α induction.

Keywords: Aryl hydrocarbon receptor; CYP1A1; Caffeic acid phenethyl ester; Hypoxia inducible factor-1α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Caffeic Acids / administration & dosage*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cytochrome P-450 CYP1A1 / metabolism*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Methylcholanthrene / administration & dosage*
  • Mice
  • Phenylethyl Alcohol / administration & dosage
  • Phenylethyl Alcohol / analogs & derivatives*

Substances

  • Caffeic Acids
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Methylcholanthrene
  • Cytochrome P-450 CYP1A1
  • caffeic acid phenethyl ester
  • Phenylethyl Alcohol