RESPONSE OF NADH OXIDATION AND GROWTH IN K-562 CELLS TO THE ANTITUMORSULFONYLUREA, N-(4-METHYLPHENYLSULFONYL)-N'-(4-CHLOROPHENYL)UREA (LY181984)

Growth of K-562 cells in culture is inhibited by the anti-tumor surfon ylureaLY181984 -(4-methylphenylsulfonyl)-N'-(4-chlorophenyl)urea) with an ED(50) of about 30 mu M. LY181984 was shown previously to inhibit NADH oxidation by plasma membranes from HeLa cells and other sources a nd to influence mitochondrial oxidative phosphorylation. With K-562 ce lls, NADH oxidation by plasma membranes was transiently stimulated and then inhibited by LY181984. NADH oxidation by whole cells was transie ntly stimulated and then inhibited by 0.1 to 100 mu M LY181984 as well . Both the stimulations and inhibitions of activity were time-dependen t. NADH oxidation by lower phase membranes depleted of plasma membrane s 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 t o be fragments of the Golgi apparatus. The oxidation of NADH by whole cells and of plasma membranes that was inhibited by LY181984 was disti nguished from mitochondrial NADH oxidation by resistance to inhibition by cyanide and by proceeding under oxygen-depleted conditions or an a rgon atmosphere. In contrast to the active antitumor agent LY181984, t he inactive but chemically-related analog, LY181984 (N-(4-methylphenyl sulfonyl)-N'-(4-phenylurea), inhibited neither growth nor NADH oxidati on with K-562 cells or cell fractions.