title: 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.
authors.affiliation: Department of Human Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770‑8503, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Ohmoto
authors.affiliation: Department of Human Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770‑8503, Japan.
authors.forename: Kazuchika
authors.initials: K
authors.lastname: Nishitsuji
authors.affiliation: Department of Human Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770‑8503, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yoshitani
authors.affiliation: Department of Human Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770‑8503, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Mizuguchi
authors.affiliation: Department of Physical Pharmaceutics, Institute of Health Biosciences and Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima 770‑8505, Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Yanagisawa
authors.affiliation: Department of Physical Pharmaceutics, Institute of Health Biosciences and Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima 770‑8505, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Saito
authors.affiliation: Department of Human Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770‑8503, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Sakashita
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000101:Acetyl-CoA C-Acetyltransferase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: C520671:(2-(4-(2-benzimidazol-2ylthio)ethyl)piperazin-1yl)-N-(2,4-bis(methylthio)-6-methyl-3-pyridyl)acetamide; D000081:Acetamides; D000970:Antineoplastic Agents; D001562:Benzimidazoles; C506639:ACAT1 protein, human; D000101:Acetyl-CoA C-Acetyltransferase; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases