TY - JOUR AB - Sulindac, a non-steroidal anti-inflammatory drug, suppresses carcinogenesis and inhibits growth of tumor cells. Pyrrolidine dithiocarbamate (PDTC), a potent NF-κB inhibitor, has been also identified as a potential anti-neoplastic agent. We hypothesized that combination of sulindac and PDTC could result in augmentation of cytotoxicity against ovarian cancer cells. The effect of sulindac and PDTC was examined on several ovarian cancer lines. Tumor cell viability was assessed using the MTT assay. Annexin-V/PI staining was used to detect apoptosis, cell cycle distribution was analyzed in FACS, and expression of cellular proteins was detected by western blotting. Incubation of OVA-14, OVP-10 and CAOV-1 ovarian cancer cells with sulindac and PDTC resulted in significantly greater inhibition of cell viability compared to either compound alone. In a model of OVA-14 cells it was evident that this effect was not related to the expression of COX enzymes since both active (sulindac sulfide) and inactive (sulindac) in vitro compounds affected the growth of tumor cells to a similar extent and synergized in cytotoxicity with PDTC. Combination of sulindac and PDTC lead to G0 arrest and massive apoptosis in co-treated cultures. Western blotting analysis argued for induction of the mitochondrial apoptotic pathway. These data demonstrate the synergistic cytotoxic effect of sulindac and PDTC on ovarian cancer cells through apoptosis and cell cycle arrest and prompt to test the efficacy of this combination in animal models. AD - Department of Immunology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland null Department of Immunology, Centre of Biostructure Research, Medical University of Warsaw, Banacha 1a Street, F building, 02-097 Warsaw, Poland AU - Jakubowska-Mućka,Anna AU - Sieńko,Jacek AU - Zapała,Łukasz AU - Wolny,Rafał AU - Lasek,Witold DA - 2012/04/01 DO - 10.3892/or.2012.1639 EP - 1250 IS - 4 JO - Oncol Rep KW - sulindac pyrrolidine dithiocarbamate ovarian cancer apoptosis PY - 2012 SN - 1021-335X 1791-2431 SP - 1245 ST - Synergistic cytotoxic effect of sulindac and pyrrolidine dithiocarbamate against ovarian cancer cells T2 - Oncology Reports TI - Synergistic cytotoxic effect of sulindac and pyrrolidine dithiocarbamate against ovarian cancer cells UR - https://doi.org/10.3892/or.2012.1639 VL - 27 ER -