PT - JOURNAL ARTICLE AU - MARTIN D. WHITE AU - LUCAS CHAN AU - JAMES W. ANTOON AU - BARBARA S. BECKMAN TI - Targeting Ovarian Cancer and Chemoresistance Through Selective Inhibition of Sphingosine Kinase-2 with ABC294640 DP - 2013 Sep 01 TA - Anticancer Research PG - 3573--3579 VI - 33 IP - 9 4099 - http://ar.iiarjournals.org/content/33/9/3573.short 4100 - http://ar.iiarjournals.org/content/33/9/3573.full SO - Anticancer Res2013 Sep 01; 33 AB - ABC294640, a selective inhibitor of sphingosine kinase-2, inhibits the formation of sphingosine 1-phosphate (S1P), a signaling lipid implicated in promoting tumor survival. We investigated the anticancer activity of ABC294640 in two ovarian cancer cell lines, BG-1 and Caov-3. ABC294640 dose-dependently inhibited clonogenic survival and cell viability of both ovarian cancer lines in vitro. Using enzyme-linked immunosorbant assays and western blot detection in chemoresistant Caov-3 cells, treatment with ABC294640 alone also potentiated bcl-2-associated X-protein and caspase-9 transcription levels, although it did not significantly increase apoptotic cell death. Interestingly, ABC294640 administered to Caov-3 ovarian cancer cells in conjunction with paclitaxel induced apoptotic cell death through activation of caspase-9. Induction of apoptosis may mediate the anticancer effect of ABC294640 in ovarian cancer, although its precise antitumor mechanism is unclear. Ultimately, through its inhibition of S1P formation and subsequent effects on critical survival signaling cascades, ABC294640 may prove to be a useful adjunct to help re-sensitize tumors to standard therapy.