Up-regulation of CYP1A1 by rutaecarpine is dependent on aryl hydrocarbon receptor and calcium

Rutaecarpine is a quinazolinocarboline alkaloid isolated from a traditional Chinese medicinal fruit, Evodia rutaecarpa. In the present study, we investigated the effect of rutaecarpine on CYP1A1 expression mediated by [Ca2+] and the AhR pathway in mouse hepatoma Hepa-1c1c7 cells. Rutaecarpine also significantly increased CYP1A1 enzyme activity and mRNA and protein levels. Rutaecarpine markedly induced XRE and AhR binding activity. CH-223191, an AhR antagonist, blocked the rutaecarpine-induced CYP1A1 enzyme activity and mRNA and protein expression. In addition, rutaecarpine remarkably induced the phosphorylation of Ca2+/calmodulin (CaM)-dependent protein kinase (CaMK). W7 and BAPTA/AM, a CaM antagonist and an intracellular Ca2+ chelator, respectively, blocked the rutaecarpine-induced CYP1A1 enzyme activity and mRNA and protein expression. These results indicate that rutaecarpine induces CYP1A1 expression through AhR- and calcium-dependent mechanisms.