Histone deacetylase inhibitors such as sodium butyrate and trichostatin A induce apoptosis through an increase of the bcl-2-related protein Bad.
The effects of sodium butyrate (SB) and trichostatin A (TSA) on cell proliferation andapoptosis against human glioma T98G, U251MG, and U877MG cells were investigated. Upon exposure to either SB or TSA, cell proliferation was reduced, and apoptosis detected by DNA fragmentation analysis and the cleavage of CPP32 was induced. Previously, we reported that SB increased the expression levels of p21 (WAF-1) and inhibited G1-S transition of the cell cycle. In this study, we showed that TSA also increased p21 expression, suggesting that histone deacetylase (HDAC) inhibitors may up-regulate p21 protein in common and thus arrest proliferation in the G1 phase of the cell cycle. To further determine the underlying molecular mechanisms of apoptosis with either SB or TSA treatment, we studied the expression levels of apoptosis-related proteins in human glioma cells. SB increased the expression of the Bad protein, although the expression of Bcl-2, Bcl-xL, Bax, and Fas was not changed by theaddition of SB. TSA treatment also up-regulated the expression of Bad protein. The results suggest that HDAC inhibitors such as SB and TSA induce apoptosis through an increase in Bad protein in human glioma cells in vitro.
Sawa
H
H
Oncology Research Center, ORC282, Hokuto Hospital, Obihiro, Hokkaido, Japan. sawa@hokuto7.or.jp
Murakami
H
H
Ohshima
Y
Y
Sugino
T
T
Nakajyo
T
T
Kisanuki
T
T
Tamura
Y
Y
Satone
A
A
Ide
W
W
Hashimoto
I
I
Kamada
H
H
D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000473:pathology; D002087:Butyrates / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000473:pathology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D012964:Sodium / Q000494:pharmacology*
D002087:Butyrates; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C012589:trichostatin A; D012964:Sodium