Amerlioration of Renal Cancer in a Mouse Model

D-threo-PDMP is an inhibitor of glucosylceramide synthase and lactosylceramide synthase. In a recent study from Dr. S Chatterjee’s laboratory from the John Hopkins University claim that mice fed with D-threo-PDMP showed marked reduction in tumor volume which was accompanied by reduction in lactosylceramide and increase in glucosylceramide level. D-threo-PDMP inhibited cell proliferation and angiogenesis by inhibiting the p44MAPK, p-AKT-1 pathway and mammalian target of rapamycin (mTOR). They further claimed “By linking glycosphingolipid synthesiswith tumor growth, renal cancer progression and regression can be evaluated. Thus inhibiting glycosphingolipid synthesis can be a bonafide target to prevent the progression of other types of cancer”.

In summary:
1. A 30-fold increase in tumor volume in mice kidney was accompanied by a 32-fold increase in the level of lactosylceramide.
2. D-threo-PDMP treatment reduced tumor volume about 50% and was not toxic to the mice.
3. Reduction in tumor volume could be due to the inhibition of angiogenesis. D-threo-PDMP did not affect apoptosis in kidney tumor.
4. D-threo-PDMP reduced ceramide mass in kidney tumors in mice as well the levels of glucose and lactosylceramide but not the level of sphingomyelin.

S. Chatterjee et al. (2013) 8(5):e63726