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-tetradecanoylphorbol 13-acetate (TPA)-induced ornithine decarboxylase mRNA steady state level and enzyme activity in mouse 308 cells (Gerhäuser et al. 1995). In MCF-7 human breast cancer cells, rotenone, deguelin and two structurally-unrelated miticides (pyridaben and fenazaquin) inhibit not only NADH: ubiquinone oxidoreductase but also induced ornithine decarboxylase activity with IC50 values of < 1 to 70 nM. Rotenone inhibits ornithine decarboxylase activity equally well as induced by TPA, insulin-like growth factor I and 17 beta-oestradiol. Pyridaben is the most potent 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 reactive oxygen species. It is therefore proposed that NADH: ubiquinone oxidoreductase inhibitors block multiple and possibly reactive oxygen species-modulated pathways which regulate ornithine decarboxylase activity.
Rowlands
J C
JC
Department of Environmental Science, Policy and Management, University of California, Berkeley 94720-3112, USA.
Casida
J E
JE
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D042967:Electron Transport Complex I; D004790:Enzyme Induction / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000096:biosynthesis* / Q000235:genetics; D011799:Quinazolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012402:Rotenone / Q000031:analogs & derivatives / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014475:Uncoupling Agents / Q000494:pharmacology*
D011799:Quinazolines; D012333:RNA, Messenger; D014475:Uncoupling Agents; D012402:Rotenone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; C087876:fenazaquin; D009247:NADH, NADPH Oxidoreductases; D009955:Ornithine Decarboxylase; D042967:Electron Transport Complex I; C107676:deguelin; D013755:Tetradecanoylphorbol Acetate