(A and B) Viability of HeLa (A) or SW620 (B) cells treated with DMSO, 800 nM YM201636, 25 μM C2-ceramide, or YM201636 plus C2-ceramide (YM + cer) for the indicated durations. (C and D) Viability of control or VAC14-overexpressing cells treated with FTY720 or C2-ceramide. Error bars indicate the mean ± SEM. (E) Vacuolation evaluated by bright-field microscopy in SW480 tumors from mice treated with vehicle (water) or 60 mg/kg SH-BC-893 by gavage daily for 18 days. Scale bar: 10 μm. (F) Tumor weight at sacrifice. P = 0.06 between vehicle and SH-BC-893–treated vector groups (2-tailed Student’s t test). Error bars indicate the mean ± SD. n ≥7 mice per group. *P < 0.05 and **P < 0.01, by unpaired, 2-tailed Student’s t test. In vitro data are representative of at least 3 independent experiments.