title: Histone deacetylase inhibitors such as sodium butyrate and trichostatin A inhibit vascular endothelial growth factor (VEGF) secretion from human glioblastoma cells.
abstract: We investigated the effects of histone deacetylase (HDAC) inhibitors such as sodium butyrate (SB) and trichostatin A (TSA) on the expression of vascular endothelial growth factor (VEGF) by human glioblastoma T98G, U251MG, and U87MG cells. The glioblastoma cells secreted three VEGF isoforms, VEGF (189), (165), and (121), although the expression levels of VEGF differed between the cell types. Treatment with either 5mM SB or 100 ng/ml TSA reduced VEGF secretion in conditioned media and reduced VEGF mRNA expression. We also studied the expression of VEGF-B, -C, and -D mRNA in human glioblastoma cells and their modulation by HDAC inhibitors. The PCR products of VEGF-B (357bp), VEGF-C (501bp), and VEGF-D (484bp) were amplified in all glioblastoma cells examined. Treatment with SB reduced the expression of VEGF-D mRNA in U251MG cells and the expression of VEGF-B mRNA in U87MG cells. TSA treatment reduced the expression of VEGF-D in U251MG cells. These results suggest that HDAC inhibitors reduce VEGF secretion and modulate the expression of the other VEGF family members, and therefore may inhibit angiogenesis in glioblastoma tissues.
authors.affiliation: Oncology Research Center, Hokuto Hospital, Kisen 7-5, Inada-cho, Obihiro, Hokkaido 080-0833, Japan. sawa@hokuto7.or.jp
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sawa
authors.forename: Hiromi
authors.initials: H
authors.lastname: Murakami
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ohshima
authors.forename: Masahiro
authors.initials: M
authors.lastname: Murakami
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yamazaki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tamura
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Mima
authors.forename: Akira
authors.initials: A
authors.lastname: Satone
authors.forename: Wataru
authors.initials: W
authors.lastname: Ide
authors.forename: Ikuo
authors.initials: I
authors.lastname: Hashimoto
authors.forename: Hajime
authors.initials: H
authors.lastname: Kamada
mesh_terms: D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism*; D002087:Butyrates / Q000494:pharmacology*; D017077:Culture Media, Conditioned; D003864:Depression, Chemical; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005909:Glioblastoma / Q000378:metabolism*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008222:Lymphokines / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D002087:Butyrates; D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C012589:trichostatin A; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases