title: Molecular and cellular effects of a novel hydroxamate-based HDAC inhibitor - belinostat - in glioblastoma cell lines: a preliminary report.
abstract: Histone deacetylase (HDAC) inhibitors are now intensively investigated as potential cytostatic agents in many malignancies. Here, we provide novel information concerning the influence of belinostat (Bel), a hydroxamate-based pan-HDAC inhibitor, on glioblastoma LN-229 and LN-18 cells. We found that LN-229 cells stimulated with 2 μmol/L of Bel for 48 h resulted in 70 % apoptosis, while equivalent treatment of LN-18 cells resulted in only 28 % apoptosis. In LN-229 cells this effect was followed by up-regulation of pro-apoptotic genes including Puma, Bim, Chop and p21. In treated LN-18 cells only p21 was markedly overexpressed. Simultaneously, LN-229 cells treated with 2 μmol/L of Bel for 48 h exhibited down-regulation of molecular chaperones GRP78 and GRP94 at the protein level. In contrast, in LN-18 cells Western blot analysis did not show any marked changes in GRP78 nor GRP94 expression. Despite noticeable overexpression of p21, there were no signs of evident G1 nor G2/M cell cycle arrest, however, the reduction in number of the S phase cells was observed in both cell lines. These results collectively suggest that Bel can be considered as potential anti-glioblastoma agent. To our knowledge this is the first report presenting the effects of belinostat treatment in glioblastoma cell lines.
authors.affiliation: Department of Pharmaceutical Biochemistry, Medical University of Białystok, Mickiewicza 2A, 15-222, Białystok, Poland. mkusaczuk@wp.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kusaczuk
authors.affiliation: Department of Pharmaceutical Biochemistry, Medical University of Białystok, Mickiewicza 2A, 15-222, Białystok, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Krętowski
authors.affiliation: Department of Pharmaceutical Biochemistry, Medical University of Białystok, Mickiewicza 2A, 15-222, Białystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Stypułkowska
authors.affiliation: Department of Pharmaceutical Biochemistry, Medical University of Białystok, Mickiewicza 2A, 15-222, Białystok, Poland.
authors.forename: Marzanna
authors.initials: M
authors.lastname: Cechowska-Pasko
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D000072224:Bcl-2-Like Protein 11 / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D000091342:Endoplasmic Reticulum Chaperone BiP; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D000072224:Bcl-2-Like Protein 11; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011518:Proto-Oncogene Proteins; D013449:Sulfonamides; D051742:Transcription Factor CHOP; D006655:Histone Deacetylases; C487081:belinostat
keywords: Apoptosis; Belinostat; Glioblastoma; Glucose regulated proteins; Histone deacetylase inhibitors