Blockade of Glycosphingolipid Synthesis Inhibits Cell Cycle and Spheroid Growth of Colon Cancer Cells In Vitro and Experimental Colon Cancer Incidence In Vivo.
Animals
Cell Cycle
/ drug effects
Colonic Neoplasms
/ chemically induced
Dioxanes
/ pharmacology
Glucosyltransferases
/ antagonists & inhibitors
Glycosphingolipids
/ biosynthesis
HCT116 Cells
Humans
Mice
Neoplasm Proteins
/ antagonists & inhibitors
Neoplasms, Experimental
/ chemically induced
Pyrrolidines
/ pharmacology
Spheroids, Cellular
/ metabolism
azoxymethane
cationic amphiphilic drugs
colorectal cancer
dextrane sulfate
glucosylceramide synthase
glycosphingolipids
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
29 Sep 2021
29 Sep 2021
Historique:
received:
31
08
2021
revised:
21
09
2021
accepted:
22
09
2021
entrez:
13
10
2021
pubmed:
14
10
2021
medline:
28
10
2021
Statut:
epublish
Résumé
Colorectal cancer (CRC) is one of the most frequently diagnosed cancers in humans. At early stages CRC is treated by surgery and at advanced stages combined with chemotherapy. We examined here the potential effect of glucosylceramide synthase (GCS)-inhibition on CRC biology. GCS is the rate-limiting enzyme in the glycosphingolipid (GSL)-biosynthesis pathway and overexpressed in many human tumors. We suppressed GSL-biosynthesis using the GCS inhibitor Genz-123346 (Genz), NB-DNJ (Miglustat) or by genetic targeting of the GCS-encoding gene UDP-glucose-ceramide-glucosyltransferase- (
Identifiants
pubmed: 34638879
pii: ijms221910539
doi: 10.3390/ijms221910539
pmc: PMC8508865
pii:
doi:
Substances chimiques
(2-(2',3'-dihydrobenzo(1,4)dioxin-6'-yl)-2-hydroxy-1-pyrrolidin-1-ylmethylethyl)nonanoic acid amide
0
Dioxanes
0
Glycosphingolipids
0
Neoplasm Proteins
0
Pyrrolidines
0
Glucosyltransferases
EC 2.4.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : SFB 1118 to H.-J.G.
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