Inhibition of Apoptosis by Nitric Oxide in MCF-7 Cells

Nitric oxide (NO) is a diffusible, multifunctional and transcellular messenger that has been implicated in numerous physiological and pathological conditions. It has been reported that NO induced apopto-sis in tumor cells, macrophage cells and inhibited apoptosis in normal cells, endothelial cells. To ex-amine whether NO could induce apoptosis in MCF-7 cells, cells were treated with SIN-1 (3-morpholinosydnonimine), NO donor. Cell viability did not change in SIN-1 treated cells for 48 h and there was no significantly changes in cell cycle progression or growth pattern by FACS analysis. But p53 protein, an apoptosis-related factor, increased SIN-1 treatment time dependently. Bcl-2, MDM2 and p21 were also accumulated. Bax level did not change. A major role of inhibiting apoptosis by NO in MCF-7 cells, cobalt chloride (CoCl2) was added to cells preincubated with SIN-1. Whereas CoCl2 treated cells underwent apoptosis, for 24 h SIN-1 preincubated cells were not induced apoptosis. Inactivated proteins, MDM2 and bcl-2, by CoCl2 levels also increased in SIN-1 pre-treated cells. These results suggested that SIN-1 blocked p53 by MDM2 activation and inhibited apoptosis by inducing p21 and bcl-2 expression