Effect of colchicine and its derivatives on the expression of selected isoforms of cytochrome P450 in primary cultures of human hepatocytes.
The study addressed the effect of colchicine and its derivatives on the protein levels of cytochrome P450 (CYP) 1A2, 2A6, 3A4, 2C9/19, and 2E1 isoforms. Primary human hepatocyte culture was the model of choice. Levels of individual CYP isoforms were detected using immunoblotting. Colchicine caused an increase of CYP2E1 protein content, colchiceine and N-deacetylcolchiceine induced isoforms CYP2C9, 2E1 and 3A4 whereas colchicoside induced CYP2C9 and 2E1. The levels of CYP1A2 and 2A6 were unaffected by any of tested compounds. Demecolcine and 3-demethylcolchicine had no effect on any studied P450 isoform. Since colchicine is an exclusive substrate of CYP3A4 whereas it induces CYP2E1, there is a suspicion rather at protein stabilization than at gene induction concerning induction origin.
Dvorák
Z
Z
Institute of Medical Chemistry and Biochemistry, Medical Faculty, Palacký University Olomouc, Hnĕvotínská 3, 77515 Olomouc, Czech Republic.
Ulrichová
J
J
Modrianský
M
M
Maurel
P
P
D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D020033:Protein Isoforms / Q000378:metabolism
D020033:Protein Isoforms; D003577:Cytochrome P-450 Enzyme System; D003078:Colchicine