Arecoline inhibits the 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cytochrome P450 1A1 activation in human hepatoma cells.
In the present study, we investigated the effect of arecoline, a major areca nut alkaloid, on the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced activation of cytochrome P4501A1 (CYP1A1) in a human hepatoma cell line Huh-7. We treated Huh-7 cells with 10nM TCDD in the presence of different concentrations of arecoline (50-300 microM). Our results indicated that arecoline attenuated the TCDD-induced CYP1A1 enzyme activation with an inhibitory effect on cell proliferation. By using real-time RT-PCR, we demonstrated that arecoline inhibited the TCDD-induced activations of CYP1A1 and AhR repressor (AhRR) mRNA expression in a similar pattern. Our results revealed that arecoline inhibited AhR mRNA expression with no direct effect on CYP1A1 enzyme activity. Therefore, in our present study, the observed inhibitory effect of arecoline on CYP1A1 activation was not due to the up-regulation of AhRR or direct inhibitory effect on CYP1A1. Taken together, here we have demonstrated that arecoline attenuates the TCDD-induced CYP1A1 activation mainly via down-regulation of AhR expression in human hepatoma cells, suggesting the possible involvement of arecoline in the AhR-mediated metabolism of environmental toxicants in liver.
Chang
Eddy Essen
EE
Laboratory of Molecular Toxicology, Division of Environmental Health and Occupational Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 35053, Taiwan.
Miao
Zhi-Feng
ZF
Lee
Wen-Jhy
WJ
Chao
How-Ran
HR
Li
Lih-Ann
LA
Wang
Ya-Fen
YF
Ko
Ying-Chin
YC
Tsai
Feng-Yuan
FY
Yeh
Szu Ching
SC
Tsou
Tsui-Chun
TC
D001114:Areca; D001115:Arecoline / Q000494:pharmacology*; D051792:Basic Helix-Loop-Helix Proteins; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics
D001115:Arecoline; D051792:Basic Helix-Loop-Helix Proteins; D019363:Cytochrome P-450 CYP1A1; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; C492162:AHRR protein, human