CCAAT/enhancer-binding protein beta activation by capsaicin contributes to the regulation of CYP1A1 expression, mediated by the aryl hydrocarbon receptor

Title
CCAAT/enhancer-binding protein beta activation by capsaicin contributes to the regulation of CYP1A1 expression, mediated by the aryl hydrocarbon receptor
Author(s)
한은희[한은희]황용필[황용필]김형균[김형균]최재호[최재호]박봉환[박봉환]송계용[송계용]이계원[이계원]정태천정혜광[정혜광]
Keywords
ENDOPLASMIC-RETICULUM STRESS; CYTOCHROME-P450 1A1; CELL-PROLIFERATION; 3-METHYLCHOLANTHRENE INDUCTION; INDUCED APOPTOSIS; HEPA-1C1C7 CELLS; ENZYMES; INHIBITION; TOXICITY; CHANNEL
Issue Date
201111
Publisher
WILEY-BLACKWELL
Citation
BRITISH JOURNAL OF PHARMACOLOGY, v.164, no.6, pp.1600 - 1613
Abstract
BACKGROUND AND PURPOSE 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. EXPERIMENTAL APPROACH 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. KEY 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 Ca2+/calmodulin (CaM)-dependent protein kinase (CaMK) and CCAAT/ enhancer-binding protein beta (C/EBP beta) activation, downstream of TRPV1 receptors. Capsaicin-induced C/EBP beta activation inhibited induction of CYP1A1 mRNA and protein by 3-MC. CONCLUSIONS AND IMPLICATIONS Capsaicin alone weakly induced CYP1A1 expression, and 3-MC-induced CYP1A1 levels were suppressed by capsaicin. Activation of C/EBP beta 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.
URI
http://hdl.handle.net/YU.REPOSITORY/24304http://dx.doi.org/10.1111/j.1476-5381.2011.01232.x
ISSN
0007-1188
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약학대학 > 약학부 > Articles
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