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Response of NADH oxidation and growth in K-562 cells to the antitumor sulfonylurea, N-(4-methylphenylsulfonyl)-N′-(4-chlorophenyl)urea (LY181984)

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Summary

Growth of K-562 cells in culture is inhibited by the antitumor sulfonylureaLY181984 (N-(4-methylphenylsulfonyl)-N′-(4-chlorophenyl)urea) with an ED50 of about 30 μM. LY181984 was shown previously to inhibit NADH oxidation by plasma membranes from HeLa cells and other sources and to influence mitochondrial oxidative phosphorylation. With K-562 cells, NADH oxidation by plasma membranes was transiently stimulated and then inhibited by LY181984. NADH oxidation by whole cells was transiently stimulated and then inhibited by 0.1 to 100 μM LY181984 as well. Both the stimulations and inhibitions of activity were time-dependent. NADH oxidation by lower phase membranes depleted of plasma membranes by aqueous two-phase partition also was inhibited by micromolar and submicromolar concentrations of LY181984. Inhibition did not correlate with mitochondrial presence but rather with membranes that appeared to be fragments of the Golgi apparatus. The oxidation of NADH by whole cells and of plasma membranes that was inhibited by LY181984 was distinguished from mitochondrial NADH oxidation by resistance to inhibition by cyanide and by proceeding under oxygen-depleted conditions or an argon atmosphere. In contrast to the active antitumor agent LY181984, the inactive but chemically-related analog, LY181985 (N-(4-methylphenyl-sulfonyl)-N′-(4-phenylurea), inhibited neither growth nor NADH oxidation with K-562 cells or cell fractions.

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Authors and Affiliations

  1. Departments of Foods and Nutrition, Purdue University, West Lafayette, Indiana

    S. Y. Moya-Camarena & D. M. Morré

  2. Department of Medicinal Chemistry, Purdue University, Arthur G. Hansen Life Sciences Research Building, 47907, West Lafayette, IN, USA

    D. J. Morré

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  1. S. Y. Moya-Camarena
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  2. D. J. Morré
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Moya-Camarena, S.Y., Morré, D.J. & Morré, D.M. Response of NADH oxidation and growth in K-562 cells to the antitumor sulfonylurea, N-(4-methylphenylsulfonyl)-N′-(4-chlorophenyl)urea (LY181984). Protoplasma 188, 151–160 (1995). https://doi.org/10.1007/BF01280366

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  • DOI: https://doi.org/10.1007/BF01280366

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