Dataset Information
A member of the Ras oncogene family, RAP1A, mediates antileishmanial activity of monastrol.
Ontology highlight
ABSTRACT: Objectives
To investigate the mode of action of monastrol in intracellular Leishmania.Methods
Microarray experiments were conducted on an Affymetrix GeneChip(®) Human Genome U133 Plus 2.0 Array, to determine the genes that encode proteins related to pathological alterations of cell signalling pathways in intracellular Leishmania amastigotes in response to monastrol treatment.Results
Monastrol induced unprenylated Rap1A in intracellular Leishmania when exposed to this anticancer drug at the IC50 (10 ?M). Monastrol, known to cause mitotic arrest in cancer cells, inhibited Rap1A prenylation (geranylgeranylation) in intracellular Leishmania, which resulted in blockade at the G1 phase of the cell cycle. Growth inhibition, rather than apoptosis, was found to be the mechanism by which monastrol displays antileishmanial activity.Conclusions
Prenylation inhibitors (unprenylation) of cell signalling pathways can be exploited in Leishmania parasites as novel therapeutic tools.
SUBMITTER: Kaur J
PROVIDER: S-EPMC3625431 | biostudies-literature | 2013 May
REPOSITORIES: biostudies-literature
Publications
A member of the Ras oncogene family, RAP1A, mediates antileishmanial activity of monastrol.
The Journal of antimicrobial chemotherapy 20130104 5
<h4>Objectives</h4>To investigate the mode of action of monastrol in intracellular Leishmania.<h4>Methods</h4>Microarray experiments were conducted on an Affymetrix GeneChip(®) Human Genome U133 Plus 2.0 Array, to determine the genes that encode proteins related to pathological alterations of cell signalling pathways in intracellular Leishmania amastigotes in response to monastrol treatment.<h4>Results</h4>Monastrol induced unprenylated Rap1A in intracellular Leishmania when exposed to this anti ...[more]
