Effects of Valproic Acid on Proliferation, Apoptosis, Angiogenesis and Metastasis of Ovarian Cancer in Vitro and in Vivo

Abstract

Inhibitors of histone deacetylase activity are emerging as a potentially important new class of anticancer agents. In this study, we assessed the anticancer effects of valproic acid (VPA) on ovarian cancer in vitro and in vivo. Cultured SKOV3 cells were treated by VPA with different concentrations and time, then the effects on cell growth, cell cycle, apoptosis, and related events were investigated. A human ovarian cancer model transplanted subcutaneously in nude mice was established, and the efficacy of VPA used alone and in combination with diammine dichloroplatinum (DDP) to inhibit the growth of tumors was also assessed. Proliferation of SKOV3 cells was inhibited by VPA in a dose and time dependent fashion. The cell cycle distribution changed one treatment with VPA, with decrease in the number of S-phase cells and increase in G1-phase. VPA could significantly inhibit the growth of the epithelial ovarian cancer SKOV3 cells in vivo without toxic side effects. Treatment with VPA combined with DDP demonstrated enhanced anticancer effects. The result of flow cytometry (FCM) indicated that after VPA in vitro and in vivo, the expression of E-cadherin was increased whereas vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were decreased. This study suggests that VPA could be a novel attractive agent for treatment of ovarian cancer.

Inhibition of Metastasis and Invasion of Ovarian Cancer Cells by Crude Polysaccharides from Rosa Roxburghii Tratt in Vitro

“…For the ovarian cancer patients at metastatic stage, there were limited effective therapies (Goff et al, 2007;Dinh et al, 2008;Jemal et al, 2008). In addition, both patients and gynecologists had to face the serious side effect of chemotherapy (Shan et al, 2012). Therefore, finding some new agents which had better anti-tumor effect without toxicities is an urgent for ovarian cancer patients.…”

Trichostatin A-induced Apoptosis is Mediated by Krüppel-like Factor 4 in Ovarian and Lung Cancer

“…Histone deacetylase inhibitors (HDACi) have emerged as a new class of targeted anticancer agents which mediates the regulation of gene expression and induces growth inhibition, apoptosis, differentiation and angiogenesis in a various of tumor cell lines (Glaser, 2007;Platta et al, 2007;Rasheed et al, 2007;Wu et al, 2007;Sonnemann et al, 2008;Bellarosa et al, 2012;Francisco et al, 2012;Shan et al, 2012;Feng et al, 2013). Owing to the high activity of HDACs in some types of cancers and reversible histone acetylation activity, HDAC has been recognized as excellent drug target for cancer therapy ( Wdcae, 2000;Weichert et al, 2008).…”

Biological Screening of Novel Derivatives of Valproic Acid for Anticancer and Antiangiogenic Properties

“…Valproic acid (VPA) has been shown to inhibit the growth of a variety of cancer cells including human hepatocellular cancer cells in vitro and in vivo (Kawagoe et al, 2002;Kaiser et al, 2006;Machado et al, 2011;Shan et al, 2012;Wang et al, 2013;Can et al, 2014). Beside an effective epileptic drug VPA also inhibits angiogenesis both in vitro and in vivo (Michaelis et al, 2004;Zgouras et al, 2004;Farooq et al, 2008;Kitazoe et al, 2009;Osuka et al, 2012).…”