RELAXIN ACTIVATES THE L-ARGININE-NITRIC OXIDE PATHWAY IN HUMAN BREAST-CANCER CELLS

Recently, we demonstrated that relaxin (RLX), a peptide hormone of ova rian origin, inhibits growth and promotes differentiation of MCF-7 bre ast adenocarcinoma cells. We also showed that RLX stimulates the produ ction of nitric oxide (NO) in several cell types. NO has been reported to have antitumor activity by inhibiting proliferation, promoting dif ferentiation, and reducing the metastatic spread of some tumor cell ty pes. In this study, we aimed at evaluating whether RLX influences the L-arginine-NO pathway in MCF-7 cells. The cells were grown in the abse nce or presence of RLX at different concentrations, and cell prolifera tion, constitutive and inducible NO synthase activities, nitrite produ ction, and intracellular levels of cyclic GMP were investigated. The r esults obtained indicate that RLX increases inducible NO synthase acti vity and potentiates NO production. This was accompanied by an elevati on of intracellular cyclic GMP, which is known to mediate the cell res ponse to NO. The RLX-induced activation of the L-arginine-NO pathway i n the MCF-7 cells was inversely related to the rate of cell proliferat ion. These results suggest that the cytostatic effect of RLX on MCF-7 breast cancer cells may rely on its ability to stimulate endogenous pr oduction of NO.