Use of a Glycolipid Inhibitor to Ameliorate Renal Cancer in a Mouse Model

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 May 15

PMID 23671696

Citations 16

Authors

Subroto Chatterjee

Nezar Alsaeedi

Jennifer Hou

Veera Venkata Ratnam Bandaru

Lan Wu

Marc K Halushka

Roberto Pili

Georges Ndikuyeze

Norman J Haughey

Affiliations

Soon will be listed here.

Abstract

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.

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