Na7CrCuW11O39.16H2O induces apoptosis in human ovarian cancer SKOV3 cells through the p38 signaling pathway

摘要

Ovarian carcinoma is a common malignant disease worldwide with a poor therapeutic response. The present study investigated the effects of Na7CrCuW11O39.16H2O (CrCuW11) on ovarian cancer cell growth and investigated the mechanisms underlying its actions. The effects of CrCuW11 on cell viability and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, acridine orange/ethidium bromide staining and electron microscopy in human ovarian cancer SKOV3 cells. The expression of bcl-2-like protein 4 (Bax), B-cell lymphoma 2 (Bcl-2), cytochrome c, phosphorylated (p)-p38 and p38 was determined by western blot analysis. Caspase-3 activity was measured by caspase-3 activity kit. CrCuW11 concentrations of 1.87×10⁻³ mol. l⁻¹ at 12 h reduced viability induced apoptosis in SKOV3 cells in a concentration-and time-dependent manner. Forced expression of CrCuW11 upregulated the expression of certain proteins (Bax, cytochrome c, and p-p38), and downregulated Bcl-2 protein expression. Furthermore, CrCuW11 also enhanced caspase-3 activity. The p38 inhibitor SB203580 was able to inhibit the activity of CrCuW11. Caspase-3 and p38 signaling pathways were associated with CrCuW11-regulated multiple targets involved in SKOV3 cell proliferation. Therefore, the results of the present study indicated that CrCuW11 may be used as a novel clinical drug for the treatment of ovarian cancer.