mice model (neuroblastoma): were treated with i.p. injection of placebo control (control) or 30 mg/kg of NSC-87877 once daily for 15 days.

To assess the potential cytotoxicity of NSC-87877, MDA-MB-468 cells were incubated in DMEM, DMEM/1% FBS, or DMEM/5% FBS and treated with 50 or 100 μM NSC-87877 for 24 h. Lactate dehydrogenase release was then used as a measure of cytotoxicity. The highest cytotoxicity value (2.9 ± 2.5%) was detected in cells treated with 100 μM NSC-87877 in DMEM/5% FBS, but it was not statistically significant (p = 0.24). Likewise, no cytotoxicity effect of NSC-87877 was observed in HEK293 cells under the same conditions. To determine whether NSC-87877 can affect cell viability, MDA-MB-468 cells cultured in DMEM/10% FBS were treated with NSC-87877 (50 μM), the Mek inhibitor U0126 (5 μM), the phosphoinositide 3-kinase inhibitor LY294002 (10 μM), and a combination of NSC-87877 and LY294002 for 4 days and the relative viable cell numbers were determined. As a result, NSC-87877, U0126, and LY294002 treatment alone significantly reduced cell viability, which corresponded to 36, 42, and 50% inhibition of 10% FBS-stimulated cell proliferation. The differences among inhibitory effects of NSC-87877, U0126, and LY294002 at the tested concentrations were not statistically significant. FBS-stimulated growth was completely inhibited by a combination of NSC-87877 and LY294002 treatment. Thus, NSC-87877 can signifi-cantly reduce MDA-MB-468 cell viability/proliferation, especially in combination with a phosphoinositide 3-kinase inhibitor.