The histone deacetylase inhibitors depsipeptide and MS-275, enhance TRAIL gene therapy of LNCaP prostate cancer cells without adverse effects in normal prostate epithelial cells.

The histone deacetylase inhibitors depsipeptide and MS-275, enhance TRAIL gene therapy of LNCaP prostate cancer cells without adverse effects in normal prostate epithelial cells. Research Abstract Details 

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The histone deacetylase inhibitors depsipeptide and MS-275, enhance TRAIL gene therapy of LNCaP prostate cancer cells without adverse effects in normal prostate epithelial cells. Abstract Text:

L Kasman,P Lu,C Voelkel-Johnson,

Gene therapy of cancer using adenovirus as a single treatment modality has met limited success and efforts to enhance therapeutic outcomes have included combination of gene therapy with chemotherapy. The goal of this study was to investigate which chemotherapeutic agents may be suitable for combination with gene therapy of prostate cancer. Using an adenovirus expressing green fluorescent protein (GFP), we determined the effect of cisplatin, gemcitabine, doxorubicin, depsipeptide and MS-275 on adenoviral infectivity and transgene expression in LNCaP cells. We found that the two histone deacetylase inhibitors (HDACi), depsipeptide and MS-275, and to a lesser extent doxorubicin, increased infectivity and transgene expression. However, only the HDACi selectively increased infectivity in LNCaP cells while doxorubicin increased infectivity to a greater extent in normal prostate epithelial cells (PrEC). The increase in infectivity but not transgene expression correlated to increased surface expression of coxsackie and adenovirus receptor (CAR). Increased transgene expression following infection with an adenovirus expressing tumor necrosis factor-related apoptosis inducing ligand (TRAIL) was observed only in LNCaP cells treated with depsipeptide or MS-275. Combination of TRAIL gene therapy with HDACi but not doxorubicin resulted in increased induction of apoptosis in LNCaP cells. In contrast, apoptosis was not enhanced by HDACi in normal PrEC. These results suggest that combination of HDACi with adenoviral TRAIL gene therapy may be a new therapeutic approach for the treatment of prostate cancer that warrants further investigation.

The histone deacetylase inhibitors depsipeptide and MS-275, enhance TRAIL gene therapy of LNCaP prostate cancer cells without adverse effects in normal prostate epithelial cells. Publishing Authors By Initials

L Kasman,P Lu,C Voelkel-Johnson,

For similar peptides: intercellular signaling peptides and proteins: cytokines: tumor necrosis factors: tnf-related apoptosis-inducing ligand research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: tumor necrosis factors: tnf-related apoptosis-inducing ligand research

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The histone deacetylase inhibitors depsipeptide and MS-275, enhance TRAIL gene therapy of LNCaP prostate cancer cells without adverse effects in normal prostate epithelial cells. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Cancer gene therapy

VOLUME: 14

Page Numbers: 327-34

Journal Abbreviation: Cancer Gene Ther.

ISSN: 0929-1903

DAY: 22

MONTH: 12

YEAR: 2006

The histone deacetylase inhibitors depsipeptide and MS-275, enhance TRAIL gene therapy of LNCaP prostate cancer cells without adverse effects in normal prostate epithelial cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9432230

The histone deacetylase inhibitors depsipeptide and MS-275, enhance TRAIL gene therapy of LNCaP prostate cancer cells without adverse effects in normal prostate epithelial cells. Keywords Mesh Terms:

KEYWORDS: TNF-Related Apoptosis-Inducing Ligand

MESH TERMS: genetics

Chemical & Substance for Abstract: The histone deacetylase inhibitors depsipeptide and MS-275, enhance TRAIL gene therapy of LNCaP prostate cancer cells without adverse effects in normal prostate epithelial cells. Information

Substance Name: Histone Deacetylases

Registry Number: EC 3.5.1.-

Grant and Affiliation Information for The histone deacetylase inhibitors depsipeptide and MS-275, enhance TRAIL gene therapy of LNCaP prostate cancer cells without adverse effects in normal prostate epithelial cells.

AFFILIATION: Department of Microbiology & Immunology, Medical University of South Carolina, Charleston, SC 29403, USA.

Country: England

AGENCY: United States NCI

GRANT: CA102218

ACRONYM: CA

MEDLINETA: Cancer Gene Ther

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