title: Caffeic acid phenethyl ester inhibits 3-MC-induced CYP1A1 expression through induction of hypoxia-inducible factor-1α.
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.
authors: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, South Korea.
authors: Hyung Gyun
authors: HG
authors: Kim
authors: Division of Life Science, Korea Basic Science Institute, Daejeon, South Korea.
authors: Eun Hee
authors: EH
authors: Han
authors: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, South Korea.
authors: Ji Hye
authors: JH
authors: Im
authors: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, South Korea.
authors: Eun Ji
authors: EJ
authors: Lee
authors: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, South Korea.
authors: Sun Woo
authors: SW
authors: Jin
authors: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, South Korea. Electronic address: hgjeong@cnu.ac.kr.
authors: Hye Gwang
authors: HG
authors: Jeong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002109:Caffeic Acids / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008748:Methylcholanthrene / Q000008:administration & dosage*; D051379:Mice; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D002109:Caffeic Acids; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008748:Methylcholanthrene; D019363:Cytochrome P-450 CYP1A1; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol
keywords: Aryl hydrocarbon receptor; CYP1A1; Caffeic acid phenethyl ester; Hypoxia inducible factor-1α