Glucosylceramide synthetase inhibitor, d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol exhibits a novel decarcinogenic activity against Shope carcinoma cells

The glucosylceramide synthetase inhibitor, d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (d-PDMP) was tested to determine whether it could exhibit anti-tumor activity against two different Shope carcinoma cell lines. The cell growth was suppressed in a dose-dependent manner in the presence of d-PDMP. This suppression seemed to be accounted for by prolongation of the lag phase and this phenomenon was especially marked in the undifferentiated cell line. The growth suppression was also partly explained by direct inhibition of cell proliferation because the suppression was released by removing the agent from the medium. The treated cells became morphologically differentiated with lower density at confluence and regained contact inhibition in flask culture. Colony-forming ability in soft agar, which has been reported to be closely correlated with tumorigenicity, was also inhibited dose-dependently in the presence of d-PDMP. These results suggested that d-PDMP could exhibit a novel decarcinogenic activity against Shope carcinoma cells.