Phosphodiesterase inhibitor, pentoxifylline enhances anticancer activity of histone deacetylase inhibitor, MS-275 in human breast cancer in vitro and in vivo

摘要: Abstract MS-275, a histone deacetylase inhibitor (HDACi), is undergoing clinical trials for treatment of various cancers. Pentoxifylline, nonselective phosphodiesterase (PDE) inhibitor, has been shown to increase the effectiveness antitumor chemotherapy. In present study, potential anti-cancer activity MS-275 in combination with pentoxifylline panel cell lines and human breast cancer xenograft model were examined. A Panel treated determine their impact on cellular proliferation, cycle regulation, apoptosis, anti-angiogenesis. The vivo activities assessed Matrigel plug angiogenesis (MDA-MB-231) model. Combination showed enhanced anti-proliferative (HCT 116, MCF-7, PC3 MDA-MB-231). Apoptotic studies performed using, Hoechst staining analysis reveal that this at lower concentrations induces apoptosis downstream HDAC inhibition PDE regulation. Further, antiangiogenic tube formation assay using HUVECs vivo. significant (P Taken together, our study demonstrated anticancer both vitro reduced toxicity. However, further are required understand mechanism effect.