INHIBITION OF PLASMA-MEMBRANE NADH OXIDASE ACTIVITY AND GROWTH OF HELA-CELLS BY NATURAL AND SYNTHETIC RETINOIDS

Several retinoids, both natural and synthetic, were evaluated for thei r ability to modulate NADH oxidase activity of plasma membranes of cul tured HeLa cells and the growth of HeLa cells in culture. Both NADH ox idase activity and the growth of cells were inhibited by the naturally -occurring retinoids all trans-retinoic acid (tretinoin) and retinol a s well as by the synthetic retinoids, trans-acitretin, 13-cis-acitreti n, etretinate and arotonoid ethylester(Ro 13-6298). For all retinoids tested, inhibition of NADH oxidase activity and inhibition of growth w ere correlated closely With tretinoin, etretinate and arotonoid ethyle ster, NADH oxidase activity and cell growth were inhibited in parallel in proportion to the logarithm of retinoid concentration over the ran ge of concentrations 10(-8) to 10(-5) M. Approximately 70% inhibition of both NADH oxidase activity and growth was reached at 10 mu M. With retinol, trans-acitretin and 13-cis-acitretin, inhibition of NADH oxid ase activity and growth also were correlated but maximum inhibition of both was about 40% at 10 mu M. The possibility is suggested that inhi bition of the plasma membrane NADH oxidase activity by retinoids may b e related to their mechanism of inhibition of growth of HeLa cells in culture.