Histone deacetylase inhibitors sensitize human colonic adenocarcinoma cell lines to TNF-related apoptosis inducing ligand-mediated apoptosis.
Int J Mol Med
; 9(5): 521-5, 2002 May.
Article
em En
| MEDLINE
| ID: mdl-11956660
ABSTRACT
Histone deacetylase inhibitor (HDAI) induces accumulation of highly acetylated histones by inhibiting the activity of histone deacetylase and inhibits cell proliferation, induces differentiation, and promotes apoptosis. TNF-related apoptosis inducing ligand (TRAIL) induces apoptosis in various human cancer cells, a promising observation because it raises the possibility of a death ligand selectively for tumor cells. However, resistance to TRAIL-induced apoptosis was seen in colonic adenocarcinoma cell lines. So we investigated whether human colonic adenocarcinoma cell lines can be sensitized to TRAIL-induced apoptosis by the addition of HDAI. We investigated sensitivity to histone deacetylase inhibitor in colonic adenocarcinoma cell lines using the MTT assay. Cell viability decreased with sodium butyrate (SB) and trichostatinA (TSA) in a dose-dependent manner in LS 180 and HT-29 cells. Nuclear condensation and fragmentation were observed by DAPI staining after 24 h stimulation with SB or TSA in LS 180 cells. We also investigated the combination of HDAI and TNF family members (TRAIL, anti-Fas antibody or TNFalpha) in colonic adenocarcinoma cell lines. HDAI augmented TNF family-related apoptosis in LS 180 cells and HT-29 cells. HDAI sensitizes human colonic adenocarcinoma cell lines to TRAIL-mediated apoptosis. HDAI may be useful as an adjuvant agent for TRAIL in the treatment of human colonic adenocarcinomas that are resistant to TRAIL.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
/
Adenocarcinoma
/
Fator de Necrose Tumoral alfa
/
Apoptose
/
Inibidores Enzimáticos
/
Inibidores de Histona Desacetilases
Limite:
Humans
Idioma:
En
Revista:
Int J Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Japão