NADH: ubiquinone oxidoreductase inhibitors block induction of ornithine decarboxylase activity in MCF-7 human breast cancer cells.

Abstract

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.

• Authors: J C Rowlands, J E Casida
• Journal: Pharmacology & toxicology (Pharmacol Toxicol) Vol. 83 Issue 5 Pg. 214-9 (Nov 1998) ISSN: 0901-9928 [Print] Denmark
• PMID: 9834970 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Quinazolines
• RNA, Messenger
• Uncoupling Agents
• Rotenone
• Estradiol
• Insulin-Like Growth Factor I
• fenazaquin
• NADH, NADPH Oxidoreductases
• Ornithine Decarboxylase
• Electron Transport Complex I
• deguelin
• Tetradecanoylphorbol Acetate

Topics

• Breast Neoplasms (drug therapy, enzymology, pathology)
• Electron Transport Complex I
• Enzyme Induction (drug effects)
• Epithelial Cells (drug effects, enzymology, pathology)
• Estradiol (pharmacology)
• Female
• Humans
• Insulin-Like Growth Factor I (pharmacology)
• NADH, NADPH Oxidoreductases (antagonists & inhibitors, metabolism)
• Ornithine Decarboxylase (biosynthesis, genetics)
• Quinazolines (pharmacology)
• RNA, Messenger (metabolism)
• Rotenone (analogs & derivatives, pharmacology)
• Tetradecanoylphorbol Acetate (pharmacology)
• Tumor Cells, Cultured
• Uncoupling Agents (pharmacology)