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.
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Authors | Rebecca L VanOosten, Jill M Moore, Bahri Karacay, Thomas S Griffith |
Journal | Cancer biology & therapy
(Cancer Biol Ther)
Vol. 4
Issue 10
Pg. 1104-12
(Oct 2005)
ISSN: 1538-4047 [Print] United States |
PMID | 16096370
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Apoptosis Regulatory Proteins
- Histone Deacetylase Inhibitors
- Membrane Glycoproteins
- RNA, Messenger
- Receptors, TNF-Related Apoptosis-Inducing Ligand
- Receptors, Tumor Necrosis Factor
- TNF-Related Apoptosis-Inducing Ligand
- TNFRSF10B protein, human
- TNFSF10 protein, human
- Tumor Necrosis Factor-alpha
- Histone Deacetylases
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Topics |
- Apoptosis
(drug effects)
- Apoptosis Regulatory Proteins
(genetics, pharmacology)
- Carcinoma, Renal Cell
(drug therapy, enzymology, genetics, pathology)
- Cell Death
(drug effects)
- Cell Line, Tumor
- Histone Deacetylase Inhibitors
- Histone Deacetylases
(classification)
- Humans
- Kidney Neoplasms
(drug therapy, enzymology, genetics, pathology)
- Membrane Glycoproteins
(genetics, pharmacology)
- RNA, Messenger
(metabolism)
- Receptors, TNF-Related Apoptosis-Inducing Ligand
- Receptors, Tumor Necrosis Factor
(metabolism)
- TNF-Related Apoptosis-Inducing Ligand
- Tumor Necrosis Factor-alpha
(genetics, pharmacology)
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