Inhibition of Ceramide Metabolism Sensitizes Human Leukemia Cells to Inhibition of BCL2-Like Proteins
Figure 5
Inhibition of sphingosine kinase synergizes with ABT-263 to kill leukemia cells by causing accumulation of ceramide and sphingosine while decreasing glucosylceramide and S1P.
(A) U937 and K562 cells were treated with single doses of ABT-263 (2 µM U937, 60 nM K562), PDMP (45 µM), SKi-II (5 µM) or combinations of the indicated concentrations of ABT-263 and PDMP or ABT-263 and SKi-II and then alamar blue was used to determine the relative cell numbers after 48 hours of treatment. (B) U937 cells were treated with ABT-263 (2 µM), SKi-II (5 µM) or the combination of both drugs from two hours. Cells were harvested, lipids were extracted and the amounts of ceramide (Cer), hexosyceramine (HexCer) and lactosylceramide (LacCer) were quantitated. (C) U937 cells were treated with ABT-263 (2 µM), SKi-II (5 µM) or the combination of both drugs for two hours. Cells were harvested, lipids were extracted and the amounts of sphingosine (Sph) and spingosine-1 phosphate (S1P) were quantitated.