Document Detail


Viability screen on pediatric low grade glioma cell lines unveils a novel anti-cancer drug of the steroid biosynthesis inhibitor family.
MedLine Citation:
PMID:  23201138     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Pediatric low grade gliomas are the most common central nervous system tumors and are still incurable among a subset of patients despite current treatment modalities. Steroid biosynthesis occurs in a wide variety of organs including the brain, to mediate an assortment of functions, including a proposed role in the growth of gliomas. Hence, targeting steroid biosynthesis and/or their signalling pathways, is anticipated as an effective approach for treating gliomas. In this study, we investigated whether our chemical library of steroid inhibitors can modulate the growth of pediatric low grade glioma cell lines (Res186, Res259, R286), and subsequently identified a potent inhibitor of 17beta-hydroxysteroid dehydrogenase type 3, referred to as DK16, which functions by attenuating cell viability, proliferation, migration/invasion and anchorage independent growth and conversely induces apoptosis and cell cycle arrest in a dose and duration dependent manner. Further investigations into the mechanisms of how DK16 functions showed that this drug increased the BAX/BCL2 expression ratio, induced phosphatidylserine externalization, and mitochondrial membrane depolarisations culminating to the release and nuclear translocation of AIF. In addition, treatments of low grade glioma cell lines with DK16 increased the expression of pro-apoptotic mediators including CDK2 and CTSL1, and with the converse diminished expression of pro-survival and migratory/invasion genes like PRKCA, TERT, MAPK8, MMP1 and MMP2. Our findings collectively demonstrate the potent anti-neoplastic properties of DK16, a steroid biosynthesis inhibitor, on the growth of pediatric low grade gliomas.
Authors:
Norbert Fonya Ajeawung; René Maltais; Chris Jones; Donald Poirier; Deepak Kamnasaran
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-28
Journal Detail:
Title:  Cancer letters     Volume:  -     ISSN:  1872-7980     ISO Abbreviation:  Cancer Lett.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-12-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ireland Ltd.
Affiliation:
Pediatrics Research Unit, CHUQ (CHUL) Research Centre, Québec, Québec, G1V 4G2, Canada.
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