K604, a specific acyl-CoA:cholesterol acyltransferase 1 inhibitor, suppresses proliferation of U251-MG glioblastoma cells

Abstract

Glioblastoma is the most aggressive type of brain tumor and has a poor prognosis. Increased levels of cholesteryl ester and simultaneous expression of acyl-CoA:cholesterol acyltransferase 1 (ACAT1) in tumor cells indicated that cholesterol esterification is critical to tumor growth. The present study confirmed that human glioblastoma tissues as well as the glioblastoma cell line U251-MG showed significant expression of ACAT1. ACAT1 expression in U251-MG cells increased in a cell proliferation-dependent manner. K604, a selective ACAT1 inhibitor, suppressed the proliferation of U251-MG cells and downregulated the activation of Akt and extracellular signal-regulated kinase in proliferating glioblastoma cells. These results suggested that ACAT1 may be a therapeutic target for the treatment of glioblastoma, with K604 as an effective therapeutic agent.