Histone deacetylase (HDAC) inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer.

Histone deacetylase (HDAC) inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Histone deacetylase (HDAC) inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer. Abstract Text:

Ling Geng,Kyle C Cuneo,Allie Fu,Tianxiang Tu,Peter W Atadja,Dennis E Hallahan,

Histone deacetylases (HDAC) have been identified as therapeutic targets due to their regulatory function in DNA structure and organization. LBH589 is a novel inhibitor of class I and II HDACs. We studied the effect of LBH589 and ionizing radiation (IR) on DNA repair in two human non-small cell lung cancer (NSCLC) cell lines (H23 and H460). gamma-H2AX foci present at DNA double-strand breaks (DSBs) were detected in the nuclei following 3 Gy irradiation for up to 6 hours. LBH589 administered before irradiation increased the duration of gamma-H2AX foci beyond 24 hours. Furthermore, radiation alone induced translocation of HDAC4 to the nucleus. In contrast, treatment with LBH589 followed by irradiation resulted in HDAC4 confinement to the cytoplasm, indicating that HDAC inhibition affects the nuclear localization of HDAC4. The findings that LBH589 confines HDAC4 to the cytoplasm and increases the duration of gamma-H2AX foci in irradiated cell lines suggest that HDAC4 participates in DNA damage signaling following IR. Annexin-propidium iodide flow cytometry assays, cell morphology studies, and cleaved caspase-3 Western blot analysis revealed a synergistic effect of LBH589 with IR in inducing apoptosis. Clonogenic survival showed a greater than additive effect when LBH589 was administered before irradiation compared with irradiation alone. In vivo tumor volume studies showed a growth delay of 20 days with combined treatment compared with 4 and 2 days for radiation or LBH589 alone. This study identifies HDAC4 as a biomarker of LBH589 activity and recognizes the ability of LBH589 to sensitize human NSCLC to radiation-induced DNA DSBs.

Histone deacetylase (HDAC) inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer. Publishing Authors By Initials

L Geng,KC Cuneo,A Fu,T Tu,PW Atadja,DE Hallahan,

For similar surgical procedures, operative: transplantation: transplantation, heterologous research abstracts see: surgical procedures, operative: transplantation: transplantation, heterologous research

PUBMED ID PMID:

MEDLINE DATE:

Histone deacetylase (HDAC) inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cancer research

VOLUME: 66

Page Numbers: 11298-304

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 1

MONTH: Dec

YEAR: 2006

Histone deacetylase (HDAC) inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2984705

Histone deacetylase (HDAC) inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer. Keywords Mesh Terms:

KEYWORDS: Transplantation, Heterologous

MESH TERMS: metabolism

Chemical & Substance for Abstract: Histone deacetylase (HDAC) inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer. Information

Substance Name: Histone Deacetylases

Registry Number: EC 3.5.1.-

Grant and Affiliation Information for Histone deacetylase (HDAC) inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer.

AFFILIATION: Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

Country: United States

AGENCY: United States NCI

GRANT: R01-CA89888

ACRONYM: CA

MEDLINETA: Cancer Res

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Histone deacetylase HDAC inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer Related Publications

• Characterization of the structure and composition of gecko adhesive setae.
• Cytosolic phospholipase A(2) regulates viability of irradiated vascular endothelium.
• Hedgehog signaling in the murine melanoma microenvironment.
• Histone deacetylase (HDAC) inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer.
• Lithium treatment prevents neurocognitive deficit resulting from cranial irradiation.
• Meta-analysis of Brain Volumes in Unaffected First-Degree Relatives of Patients With Schizophrenia Overemphasizes Hippocampal Deficits.
• Noninvasive assessment of cancer response to therapy.
• Noninvasive assessment of tumor vasculature response to radiation-mediated, vasculature-targeted therapy using quantified power Doppler sonography: implications for improvement of therapy schedules.
• Radiation-guided P-selectin antibody targeted to lung cancer.
• Unrelated cord blood transplantation in a girl with Hoyeraal-Hreidarsson syndrome.