Isotype-Specific Inhibition of Histone Deacetylases: Identification of Optimal Targets for Radiosensitization / Journal of the Korean Cancer Association, 대한암학회지
Cancer Research and Treatment
;
: 1130-1140, 2016.
Artigo
em Inglês
| WPRIM
| ID: wpr-68881
ABSTRACT
PURPOSE:
Histone deacetylase (HDAC) inhibitors radiosensitize tumor cells. To elucidate mechanisms underlying radiosensitization by HDAC inhibition, understanding of differential contributions of HDAC isotypes is needed. The aim of this study was to investigate involvement of known HDAC isotypes in modulation of cellular radiosensitivity. MATERIALS ANDMETHODS:
Because pharmacologic HDAC inhibitors lack isotype-specificity, RNA interference against 11 HDAC isotypes was used to inhibit HDAC in an isotype-specific manner. Radiation cell survival was evaluated using a clonogenic assay in SQ20B cells transfected with small interfering RNA specifically targeting HDAC isotypes. Immunocytochemistry was performed for detection of γH2AX foci. Protein expression was measured using Western blotting.RESULTS:
Among 11 HDAC isotypes tested, specific inhibition of 7 isotypes (HDAC1, HDAC3, HDAC4, HDAC6, HDAC7, HDAC10, and HDAC11) enhanced radiation lethality in SQ20B cells. Radiosensitization by inhibition of these HDAC isotypes was accompanied by delay of DNA double strand break repair. Radiosensitivity of SQ20B cells was not altered by selective inhibition of the remaining four isotypes (HDAC2, HDAC5, HDAC8, and HDAC9). Inhibition of HDAC isotypes resulted in downregulation of various proteins involved in pro-survival and DNA damage repair pathways.CONCLUSION:
Isotype-specificity exists in HDAC inhibition-induced radiosensitization. Different HDAC isotypes are differentially involved in modulation of cellular radiosensitivity.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Radiação Ionizante
/
Tolerância a Radiação
/
Dano ao DNA
/
DNA
/
Imuno-Histoquímica
/
Histonas
/
Regulação para Baixo
/
Sobrevivência Celular
/
Western Blotting
/
RNA Interferente Pequeno
Tipo de estudo:
Estudo diagnóstico
Idioma:
Inglês
Revista:
Cancer Research and Treatment
Ano de publicação:
2016
Tipo de documento:
Artigo
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