Published in Cancer Detection and Prevention 1993; 17(1).
The new immunosuppressive agent scoparone mediated cytochrome P450 enzyme induction in long-term cell cultures of morris hepatoma (MH(1)C(1)) cells*Abt. Anatomie and Abt. Physiologische Chemie, Univ Ulm, FRG
and has therefore a better beneficial effect than the immunosuppressivum cyclosporin A. The metabolism of scoparone, has been studied extensively in our laboratory. In this study we examined the influence of scoparone and esculetin on the cytochrome P450 enzyme activities in long-term cultured Morris hepatoma. cells (MH(1)C(1)). The cells grown as monolayers after eight days of culture and exposed to scoparone (0.1 mM) or esculetin (0.1 mM) for four more days, showed in both cases a 100% enhancement of the scoparone-o-demethylase activity compared to controls. Immunological characterization of individual P450 enzymes in the MH(1)C(1) showed an enhancement of the P4501A1. Scoparone and the product esculetin induce the scoparone- metabolizing P450 enzyme. Since the catechol esculetin can readily oxidized to its o-quinone which bind to cell proteins (enzymes, cytokines, antibodies) the immunosuppressive activity of scoparone can be due to cytokine-o-quinone-adducts which suppress the release of cytokines from T-lymphocytes.
Paper presented at the International Symposium on Cofactor Interactions and Cancer Prevention; Nice, France; March 17-19, 1993; in the section on Therapeutic Approaches.