Histone Deacetylase Inhibition Attenuates Cell Growth with Associated Telomerase Inhibition in High-Grade Childhood Brain Tumor Cells

Research output: Contribution to journalArticle

Standard

Histone Deacetylase Inhibition Attenuates Cell Growth with Associated Telomerase Inhibition in High-Grade Childhood Brain Tumor Cells. / Rahman, R; Osteso-Ibanez, T; Hirst, RA; Levesley, J; Kilday, JP; Quinn, S; Peet, Andrew; O'Callaghan, C; Coyle, B; Grundy, RG.

In: Molecular Cancer Therapeutics, Vol. 9, No. 9, 01.09.2010, p. 2568-2581.

Research output: Contribution to journalArticle

Harvard

Rahman, R, Osteso-Ibanez, T, Hirst, RA, Levesley, J, Kilday, JP, Quinn, S, Peet, A, O'Callaghan, C, Coyle, B & Grundy, RG 2010, 'Histone Deacetylase Inhibition Attenuates Cell Growth with Associated Telomerase Inhibition in High-Grade Childhood Brain Tumor Cells', Molecular Cancer Therapeutics, vol. 9, no. 9, pp. 2568-2581. https://doi.org/10.1158/1535-7163.MCT-10-0272

APA

Rahman, R., Osteso-Ibanez, T., Hirst, RA., Levesley, J., Kilday, JP., Quinn, S., Peet, A., O'Callaghan, C., Coyle, B., & Grundy, RG. (2010). Histone Deacetylase Inhibition Attenuates Cell Growth with Associated Telomerase Inhibition in High-Grade Childhood Brain Tumor Cells. Molecular Cancer Therapeutics, 9(9), 2568-2581. https://doi.org/10.1158/1535-7163.MCT-10-0272

Vancouver

Author

Rahman, R ; Osteso-Ibanez, T ; Hirst, RA ; Levesley, J ; Kilday, JP ; Quinn, S ; Peet, Andrew ; O'Callaghan, C ; Coyle, B ; Grundy, RG. / Histone Deacetylase Inhibition Attenuates Cell Growth with Associated Telomerase Inhibition in High-Grade Childhood Brain Tumor Cells. In: Molecular Cancer Therapeutics. 2010 ; Vol. 9, No. 9. pp. 2568-2581.

Bibtex

@article{8336fa4d40544068934560f54c89291d,
title = "Histone Deacetylase Inhibition Attenuates Cell Growth with Associated Telomerase Inhibition in High-Grade Childhood Brain Tumor Cells",
abstract = "Aberrant epigenetic regulation of gene expression contributes to tumor initiation and progression. Studies from a plethora of hematologic and solid tumors support the use of histone deacetylase inhibitors (HDACi) as potent anticancer agents. However, the mechanism of HDACi action with respect to the temporal order of induced cellular events is unclear. The present study investigates the anticancer effects of the HDACi trichostatin A in high-grade childhood brain tumor cells. Acute exposure to trichostatin A resulted in marked inhibition of cell proliferation, an increase in the proportion of G(2)-M cells, activation of H2A.X, and subsequent induction of apoptosis in the majority of cell lines. These phenotypic effects were associated with abrogation of telomerase activity and human telomerase reverse transcriptase downregulation in the majority of cell lines. In contrast, no cytotoxicity was observed in primary ependymal cells with respect to cilia function. Thus, inhibition of histone deacetylases leads to antiproliferative and proapoptotic effects in childhood brain tumor cells, likely to involve altered chromatin regulation at the human telomerase reverse transcriptase promoter. Mol Cancer Ther; 9(9); 2568-81. (C) 2010 AACR.",
author = "R Rahman and T Osteso-Ibanez and RA Hirst and J Levesley and JP Kilday and S Quinn and Andrew Peet and C O'Callaghan and B Coyle and RG Grundy",
year = "2010",
month = sep,
day = "1",
doi = "10.1158/1535-7163.MCT-10-0272",
language = "English",
volume = "9",
pages = "2568--2581",
journal = "Molecular Cancer Therapeutics",
issn = "1535-7163",
publisher = "American Association for Cancer Research",
number = "9",

}

RIS

TY - JOUR

T1 - Histone Deacetylase Inhibition Attenuates Cell Growth with Associated Telomerase Inhibition in High-Grade Childhood Brain Tumor Cells

AU - Rahman, R

AU - Osteso-Ibanez, T

AU - Hirst, RA

AU - Levesley, J

AU - Kilday, JP

AU - Quinn, S

AU - Peet, Andrew

AU - O'Callaghan, C

AU - Coyle, B

AU - Grundy, RG

PY - 2010/9/1

Y1 - 2010/9/1

N2 - Aberrant epigenetic regulation of gene expression contributes to tumor initiation and progression. Studies from a plethora of hematologic and solid tumors support the use of histone deacetylase inhibitors (HDACi) as potent anticancer agents. However, the mechanism of HDACi action with respect to the temporal order of induced cellular events is unclear. The present study investigates the anticancer effects of the HDACi trichostatin A in high-grade childhood brain tumor cells. Acute exposure to trichostatin A resulted in marked inhibition of cell proliferation, an increase in the proportion of G(2)-M cells, activation of H2A.X, and subsequent induction of apoptosis in the majority of cell lines. These phenotypic effects were associated with abrogation of telomerase activity and human telomerase reverse transcriptase downregulation in the majority of cell lines. In contrast, no cytotoxicity was observed in primary ependymal cells with respect to cilia function. Thus, inhibition of histone deacetylases leads to antiproliferative and proapoptotic effects in childhood brain tumor cells, likely to involve altered chromatin regulation at the human telomerase reverse transcriptase promoter. Mol Cancer Ther; 9(9); 2568-81. (C) 2010 AACR.

AB - Aberrant epigenetic regulation of gene expression contributes to tumor initiation and progression. Studies from a plethora of hematologic and solid tumors support the use of histone deacetylase inhibitors (HDACi) as potent anticancer agents. However, the mechanism of HDACi action with respect to the temporal order of induced cellular events is unclear. The present study investigates the anticancer effects of the HDACi trichostatin A in high-grade childhood brain tumor cells. Acute exposure to trichostatin A resulted in marked inhibition of cell proliferation, an increase in the proportion of G(2)-M cells, activation of H2A.X, and subsequent induction of apoptosis in the majority of cell lines. These phenotypic effects were associated with abrogation of telomerase activity and human telomerase reverse transcriptase downregulation in the majority of cell lines. In contrast, no cytotoxicity was observed in primary ependymal cells with respect to cilia function. Thus, inhibition of histone deacetylases leads to antiproliferative and proapoptotic effects in childhood brain tumor cells, likely to involve altered chromatin regulation at the human telomerase reverse transcriptase promoter. Mol Cancer Ther; 9(9); 2568-81. (C) 2010 AACR.

U2 - 10.1158/1535-7163.MCT-10-0272

DO - 10.1158/1535-7163.MCT-10-0272

M3 - Article

C2 - 20643785

VL - 9

SP - 2568

EP - 2581

JO - Molecular Cancer Therapeutics

JF - Molecular Cancer Therapeutics

SN - 1535-7163

IS - 9

ER -