NONOates: Short-acting spermine/NO and long-acting diethylenetriamine/NO, exert cytotoxic and growth inhibition effects on SK-OV-3 and OVCAR 3 cancer cell lines

Abstract

Nitric oxide (NO) is an inorganic, highly reactive, free radical with varied biological functions. It’s ability to act both, as pro-neoplastic and anti-neoplastic agent, depending on the concentration in the microenvironment, is widely known. Because of its increasing potential in cancer treatment, there is constant development of NO donor drugs. Among all other, one of the most promising are NONOates, due to predictable amount of NO they release.The aim of this study was the evaluation of growth inhibiting and cytotoxic effect of two members of NONOates family with different half-life times: spermine/NO (SPER/NO) and diethylenetriamine/NO (DETA/NO), on SK-OV-3 and OVCAR 3 ovarian cancer cell lines. Both cell lines are of epithelial origin and were acquired from metastatic tumor. The 10, 100, 1000 μM compound concentrations were added to cell cultures medium and cells were incubated for 24–48 h (SPER/NO) and 48–96 h (DETA/NO). The growth inhibition and cytotoxicity were determined using: MTT, propidium iodide exclusion and lactate dehydrogenase tests. Cell proliferation was also evaluated using WST8 assay. This study show that both, SPER/NO and DETA/NO, in the time and concentration dependent manners inhibit growth and proliferation of SK-OV-3 and OVCAR 3. However, cell lines differ in the sensitivity to NO donors. Long-acting DETA/NO has stronger inhibiting effect on the growth of ovarian cancer cell lines than short-acting SPER/NO. We also found that both donors have low but significant cytotoxic activity against ovarian cancer cells. Our results indicate that NO donors have potential anti-cancer activity. Supporting: Grant NN407095840.