Open AccessUse of a Glycolipid Inhibitor to Ameliorate Renal Cancer in a Mouse Model
Author(s) -
Subroto Chatterjee,
Nezar Alsaeedi,
Jennifer C. Hou,
Veera Venkata Ratnam Bandaru,
Lan Wu,
Marc K. Halushka,
Роберто Пили,
Georges Habineza Ndikuyeze,
Norman J. Haughey
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0063726
Subject(s) - lactosylceramide , glycosphingolipid , globotriaosylceramide , cancer , cancer research , pi3k/akt/mtor pathway , chemistry , tumor progression , angiogenesis , sphingolipid , cell growth , medicine , glycolipid , endocrinology , biology , pharmacology , biochemistry , signal transduction , fabry disease , disease
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.