Acyl-coenzyme A: cholesterol acyltransferase inhibitor Avasimibe affect survival and proliferation of glioma tumor cell lines.
Glioblastoma is the most common primary brain tumor in adults and one of its hallmarks is resistance to apoptosis. Acyl-CoA: cholesterol acyltransferase (ACAT) is an intracellular membrane-bound enzyme that uses cholesterol and long chain fatty acyl-CoA as substrates to produce cholesteryl esters. The presence of cholesteryl esters in glioblastoma may be related to vascular and/or cell neoplastic proliferation in the tumor mass, two prerequisites for tumor cell growth. ACAT activity has been detected in glioblastoma cell homogenates. The present study is the first report on the effect of Avasimibe, a specific inhibitor of ACAT, on glioma cell lines (U87, A172 and GL261). Our results showed that Avasimibe inhibited ACAT-1 expression and cholesterol ester synthesis in glioma cell lines. Moreover, Avasimibe inhibited the growth of the cells by inducing cell cycle arrest and induced apoptosis as a result of caspase-8 and caspase-3 activation. Also, Our findings provide proof of principle that targeting ACAT-1 with the inhibitor Avasimibe could be an efficient therapy in the treatment of glioblastoma.
Bemlih
Sana
S
Laboratory of Immuno-Oncology and Cancer Immunotherapy, Immunology Program, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada.
Poirier
Marie-Denise
MD
El Andaloussi
Abdeljabar
A
D000081:Acetamides; D000085:Acetates / Q000494:pharmacology*; D000101:Acetyl-CoA C-Acetyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002788:Cholesterol Esters / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D013449:Sulfonamides; D013451:Sulfonic Acids / Q000494:pharmacology*
D000081:Acetamides; D000085:Acetates; D000970:Antineoplastic Agents; D002788:Cholesterol Esters; D004791:Enzyme Inhibitors; D013449:Sulfonamides; D013451:Sulfonic Acids; C423185:avasimibe; C506639:ACAT1 protein, human; D000101:Acetyl-CoA C-Acetyltransferase