title: Phenylbutyrate-a pan-HDAC inhibitor-suppresses proliferation of glioblastoma LN-229 cell line.
abstract: Phenylbutyrate (PBA) is a histone deacetylase inhibitor known for inducing differentiation, cell cycle arrest, and apoptosis in various cancer cells. However, the effects of PBA seem to be very cell-type-specific and sometimes limited exclusively to a particular cell line. Here, we provided novel information concerning cellular effects of PBA in LN-229 and LN-18 glioblastoma cell lines which have not been previously evaluated in context of PBA exposure. We found that LN-18 cells were PBA-insensitive even at high concentrations of PBA. In contrary, in LN-229 cells, 5 and 15 mmol/L PBA inhibited cell growth and proliferation mainly by causing prominent changes in cell morphology and promoting S- and G2/M-dependent cell cycle arrest. Moreover, we observed nearly a 3-fold increase in apoptosis of LN-229 cells treated with 15 mmol/L PBA, in comparison to control. Furthermore, PBA was found to up-regulate the expression of p21 whereas p53 expression level remained unchanged. We also showed that PBA down-regulated the expression of the anti-apoptotic genes Bcl-2/Bcl-X L , however without affecting the expression of pro-apoptotic Bax and Bim. Taken together, our results suggest that PBA might potentially be considered as an agent slowing-down the progress of glioblastoma; however, further analyses are still needed to comprehensively resolve the nature of its activity in this type of cancer.
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 Microbiology, Institute of Biology, University of Białystok, Białystok, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Bartoszewicz
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; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D010654:Phenylbutyrates / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D010654:Phenylbutyrates
keywords: Apoptosis; Cell cycle; Glioblastoma; Histone deacetylase inhibitors; Phenylbutyrate