Histone deacetylase inhibitors modulate renal cell carcinoma sensitivity to TRAIL/Apo-2L-induced apoptosis by enhancing TRAIL-R2 expression

Rebecca L VanOosten; Jill M Moore; Bahri Karacay; Thomas S Griffith

doi:10.4161/cbt.4.10.2022

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Histone deacetylase inhibitors modulate renal cell carcinoma sensitivity to TRAIL/Apo-2L-induced apoptosis by enhancing TRAIL-R2 expression

Journal article

Open access

Peer reviewed

Histone deacetylase inhibitors modulate renal cell carcinoma sensitivity to TRAIL/Apo-2L-induced apoptosis by enhancing TRAIL-R2 expression

Rebecca L VanOosten, Jill M Moore, Bahri Karacay and Thomas S Griffith

Cancer biology & therapy, Vol.4(10), pp.1104-1112

10/2005

DOI: 10.4161/cbt.4.10.2022

PMID: 16096370

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Abstract

Every year, 12,000 people in the U.S. die from renal cell carcinoma. Current therapies include partial or complete nephrectomy or treatments such as administration of IFN-alpha and/or interleukins that are moderately effective, at best. Moreover, the current therapies are invasive and inefficient and new therapies are needed. Histone deacetylase (HDAC) inhibitors have recently been found to sensitize cells to apoptosis-inducing agents, although the mechanism of this action is largely unknown. The current study has investigated the potential of using five different histone deacetylase inhibitors (HDACI) (depsipeptide, MS-275, oxamflatin, sodium butyrate, and trichostatin A) to sensitize TNF-related apoptosis-inducing ligand (TRAIL)/Apo-2L-resistant renal cell carcinoma cells to TRAIL/Apo-2L-induced apoptosis. Sodium butyrate and trichostatin A each enhanced TRAIL/Apo-2L-mediated tumor cell death to a greater extent than the other HDACI. Annexin V staining and caspase activity demonstrated the mechanism of cell death was apoptosis. Both sodium butyrate and trichostatin A treatment also increased mRNA and surface expression of TRAIL receptor 2 that was dependent on the transcription factor Sp1, thus providing a possible mechanism behind the increased sensitivity to TRAIL/Apo-2L. These results indicate that combination therapy of HDACI, such as sodium butyrate and trichostatin A, and TRAIL/Apo-2L has great potential for an efficient alternative therapy for renal cell carcinoma.

Receptors, Tumor Necrosis Factor - metabolism

Kidney Neoplasms - genetics

Apoptosis Regulatory Proteins - pharmacology

Apoptosis - drug effects

Carcinoma, Renal Cell - pathology

Humans

Membrane Glycoproteins - pharmacology

Tumor Necrosis Factor-alpha - genetics

Carcinoma, Renal Cell - genetics

RNA, Messenger - metabolism

Receptors, TNF-Related Apoptosis-Inducing Ligand

Membrane Glycoproteins - genetics

Tumor Necrosis Factor-alpha - pharmacology

Histone Deacetylases - classification

TNF-Related Apoptosis-Inducing Ligand

Kidney Neoplasms - enzymology

Apoptosis Regulatory Proteins - genetics

Cell Line, Tumor

Carcinoma, Renal Cell - enzymology

Kidney Neoplasms - pathology

Histone Deacetylase Inhibitors

Cell Death - drug effects

Carcinoma, Renal Cell - drug therapy

Kidney Neoplasms - drug therapy

Details

Title: Subtitle: Histone deacetylase inhibitors modulate renal cell carcinoma sensitivity to TRAIL/Apo-2L-induced apoptosis by enhancing TRAIL-R2 expression
Creators: Rebecca L VanOosten - Department of Urology, University of Iowa, Iowa City, Iowa 52242-1089, USA
Jill M Moore
Bahri Karacay
Thomas S Griffith
Resource Type: Journal article
Publication Details: Cancer biology & therapy, Vol.4(10), pp.1104-1112
Publisher: United States
DOI: 10.4161/cbt.4.10.2022
PMID: 16096370
ISSN: 1538-4047
eISSN: 1555-8576
Grant note: CA109446-01 / NCI NIH HHS 2 P50 DK052617-06A1 / NIDDK NIH HHS
Language: English
Date published: 10/2005
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute
Record Identifier: 9984065830202771

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