Arsenic trioxide and tetraarsenic oxide induce cytotoxicity and have a synergistic effect with cisplatin in paclitaxel-resistant ovarian cancer cells

Background: Arsenic compounds (As 2 O 3 and As 4 O 6 ) have demonstrated anticancer effects in various malignancies. In this study, the cytotoxicity of arsenic compounds on ovarian cancer cell lines and the anticancer activity of the combination of arsenic compounds and cisplatin IN chemoresistant ovarian cancer cells were investigated. Methods: We investigated the cytotoxicity of As 2 O 3 and As 4 O 6 and their combinations with cisplatin in the paclitaxel-sensitive ovarian cancer cell lines SKOV3ip1 and HeyA8 and paclitaxel-resistant ovarian cancer cell lines SKOV3TRip2 and HeyA8-MDR. Growth and apoptosis were evaluated by MTT assay and annexin V assay using flow cytometry, respectively. For detection of apoptotic cells, immunofluorescence was performed using a cleaved caspase-3 antibody. Cell-cycle distribution was determined by propidium iodide staining and flow cytometry. Results: Treatment of each cell line with As 2 O 3 or As 4 O 6 led to a marked dose-dependent inhibition of cell growth. As 2 O 3 and As 4 O 6 treatment induced caspase-3-dependent apoptosis in all cell lines compared to the respective control groups (p