Use of a Glycolipid Inhibitor to Ameliorate Renal Cancer in a Mouse ModelReportar como inadecuado

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In a xenograft model wherein, live renal cancer cells were implanted under the kidney capsule in mice, revealed a 30-fold increase in tumor volume over a period of 26 days and this was accompanied with a 32-fold increase in the level of lactosylceramide LacCer. Mice fed D- threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol D-PDMP, an inhibitor of glucosylceramide synthase and lactosylceramide synthase LCS: β-1,4-GalT-V, showed marked reduction in tumor volume. This was accompanied by a decrease in the mass of lactosylceramide and an increase in glucosylceramide GlcCer level. Mechanistic studies revealed that D-PDMP inhibited cell proliferation and angiogenesis by inhibiting p44MAPK, p-AKT-1 pathway and mammalian target for rapamycin mTOR. By linking glycosphingolipid synthesis with 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.

Autor: Subroto Chatterjee , Nezar Alsaeedi, Jennifer Hou, Veera Venkata Ratnam Bandaru, Lan Wu, Marc K. Halushka, Roberto Pili, Georges



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