Synergistic antitumor effects of histone deacetylase inhibitor scriptaid and bortezomib against ovarian cancer cells.

Despite debulking surgery and good initial response to chemotherapy, the majority of patients with advanced ovarian cancer relapse and succumb to their disease. Thus, there is a pressing need to improve treatment outcome. In the present study, the antitumor activity of histone deacetylase (HDAC) inhibitor scriptaid in combination with bortezomib or conventional chemotherapeutics was tested in vitro against representative ovarian cancer cell lines: SKOV-3, MDAH 2774, and OVP-10. Incubation of ovarian cancer cells with scriptaid and bortezomib (or doxorubicin) led to synergistic antitumor effects. As shown in the Annexin V-FITC/PI assay and western blot analysis of caspase-3/-9 and p21 protein expression, these synergistic antitumor effects were due to both induction of apoptosis and inhibition of proliferation. Since synergistic antitumor activity of scriptaid and bortezomib appeared in suboptimal concentrations, one can assume that the administration of the combination of these agents to ovarian cancer patients can exert the therapeutic effect in parallel with limited general toxicity of the treatment.