NADH-UBIQUINONE OXIDOREDUCTASE INHIBITORS BLOCK INDUCTION OF ORNITHINE DECARBOXYLASE ACTIVITY IN MCF-7 HUMAN BREAST-CANCER CELLS

Rotenone is the classical inhibitor of NADH:ubiquinone oxidoreductase and its analogue deguelin is a potent inhibitor of 12-O-tetradecanoylp horbol 13-acetate (TPA)-induced ornithine decarboxylase mRNA steady st ate level and enzyme activity in mouse 308 cells (Gerhauser et al. 199 5). In MCF-7 human breast cancer cells, rotenone, deguelin and two str ucturally-unrelated miticides (pyridaben and fenazaquin) inhibit not o nly NADH:ubiquinone oxidoreductase but also induced ornithine decarbox ylase activity with IC50 values of <1 to 70 nM. Rotenone inhibits orni thine decarboxylase activity equally well as induced by TPA, insulin-l ike growth factor I and 17 beta-oestradiol. Pyridaben is the most pote nt of the four inhibitors not only for NADH:ubiquinone oxidoreductase activity (bovine heart enzyme) and TPA-induced ornithine decarboxylase activity and mRNA steady state level but also for TPA-induced reactiv e oxygen species. It is therefore proposed that NADH:ubiquinone oxidor eductase inhibitors block multiple and possibly reactive oxygen specie s-modulated pathways which regulate ornithine decarboxylase activity.