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

Subroto Chatterjee, Nezar Alsaeedi, Jennifer Hou, Veera Venkata Ratnam Bandaru, Lan Wu, Marc K. Halushka, Roberto Pili, Georges Ndikuyeze, Norman J. Haughey

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish (US)
Article numbere63726
JournalPLoS ONE
Volume8
Issue number5
DOIs
StatePublished - May 9 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Chatterjee, S., Alsaeedi, N., Hou, J., Bandaru, V. V. R., Wu, L., Halushka, M. K., Pili, R., Ndikuyeze, G., & Haughey, N. J. (2013). Use of a Glycolipid Inhibitor to Ameliorate Renal Cancer in a Mouse Model. PLoS ONE, 8(5), [e63726]. https://doi.org/10.1371/journal.pone.0063726