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: Magdalena Kusaczuk, Rafał Krętowski, Anna Stypułkowska, Marzanna Cechowska-Pasko
• Journal: Investigational new drugs (Invest New Drugs) Vol. 34 Issue 5 Pg. 552-64 (10 2016) ISSN: 1573-0646 [Electronic] United States
• PMID: 27468826 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Apoptosis Regulatory Proteins
• BBC3 protein, human
• Bcl-2-Like Protein 11
• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• DDIT3 protein, human
• Endoplasmic Reticulum Chaperone BiP
• HSPA5 protein, human
• Histone Deacetylase Inhibitors
• Hydroxamic Acids
• Proto-Oncogene Proteins
• Sulfonamides
• Transcription Factor CHOP
• Histone Deacetylases
• belinostat

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (genetics)
• Bcl-2-Like Protein 11 (genetics)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cyclin-Dependent Kinase Inhibitor p21 (genetics)
• Endoplasmic Reticulum Chaperone BiP
• Gene Expression Regulation, Neoplastic (drug effects)
• Glioblastoma (drug therapy, genetics, metabolism)
• Histone Deacetylase Inhibitors (pharmacology)
• Histone Deacetylases (metabolism)
• Humans
• Hydroxamic Acids (pharmacology)
• Proto-Oncogene Proteins (genetics)
• Sulfonamides (pharmacology)
• Transcription Factor CHOP (genetics)