NADH: Ubiquinone Oxidoreductase Inhibitors Block Induction of Ornithine Decarboxylase Activity in MCF‐7 Human Breast Cancer Cells*

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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 (Gerhäuseret 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 IC50values of <1 to 70 nM. Rotenone inhibits ornithine decarboxylase activity equally well as induced by TPA, insulin‐like growth factor I and 17β‐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.

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