CCAAT/ enhancer-binding protein β activation by capsaicin contributes to the regulation of CYP1A1 expression, mediated by the aryl hydrocarbon receptor.
OBJECTIVE
Capsaicin, a constituent of peppers, has been linked to the suppression of tumorigenesis and carcinogenesis. The influence of capsaicin on cytochrome P450 (CYP) 1A1, which is involved in metabolism of carcinogens, and the underlying mechanisms remain unclear. Here, we examined the effect of capsaicin on CYP1A1 expression in mouse hepatoma cells.


METHODS
Murine hepatoma Hepa-1c1c7 cells were incubated with capsaicin and/or 3-methylcholanthrene (3-MC). Effects of capsaicin on CYP1A1 levels were determined by analysing mRNA expression, transcription activity and protein expression. Regulation of CYP1A1 was investigated by determining transcriptional factor expression, activation and binding activity with cotreatment with target signal antagonists.


RESULTS
Capsaicin alone slightly induced CYP1A1 activity, mRNA expression, protein level and promoter activity. Treatment with transient receptor potential vanilloid type-1 receptor (TRPV1) or aryl hydrocarbon receptor (AhR) antagonist decreased induction of CYP1A1 expression by capsaicin. Additionally, capsaicin significantly inhibited 3-MC-induced CYP1A1 mRNA and protein level and xenobiotic response element-luciferase activity. Capsaicin also inhibited 3-MC-induced AhR transactivation and nuclear localization of AhRs. Moreover, capsaicin increased Ca(2+) /calmodulin (CaM)-dependent protein kinase (CaMK) and CCAAT/ enhancer-binding protein β (C/EBPβ) activation, downstream of TRPV1 receptors. Capsaicin-induced C/EBPβ activation inhibited induction of CYP1A1 mRNA and protein by 3-MC.


CONCLUSIONS
Capsaicin alone weakly induced CYP1A1 expression, and 3-MC-induced CYP1A1 levels were suppressed by capsaicin. Activation of C/EBPβ and inhibition of 3-MC-induced AhR transactivation by capsaicin contributed to the suppression of CYP1A1 expression. Capsaicin has a potential chemopreventive effect through inhibiting induction of CYP1A1 by poly aryl hydrocarbons.
Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, South Korea.
Eun Hee
EH
Han
Yong Pil
YP
Hwang
Hyung Gyun
HG
Kim
Jai Ho
JH
Choi
Bong Hwan
BH
Park
Gye Yong
GY
Song
Gye Won
GW
Lee
Tae Cheon
TC
Jeong
Hye Gwang
HG
Jeong
D000818:Animals; D001551:Benz(a)Anthracenes / Q000494:pharmacology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008748:Methylcholanthrene; D051379:Mice; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050916:TRPV Cation Channels / Q000096:biosynthesis
D001551:Benz(a)Anthracenes; D022782:CCAAT-Enhancer-Binding Protein-beta; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D008748:Methylcholanthrene; D019363:Cytochrome P-450 CYP1A1; D002211:Capsaicin
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