Depsipeptide (FR901228) inhibits proliferation and induces apoptosis in primary and metastatic human uveal melanoma cell lines.

Depsipeptide (FR901228) inhibits proliferation and induces apoptosis in primary and metastatic human uveal melanoma cell lines. Research Abstract Details 

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Depsipeptide (FR901228) inhibits proliferation and induces apoptosis in primary and metastatic human uveal melanoma cell lines. Abstract Text:

PURPOSE: Uveal melanoma (UM) is the most common primary malignant ocular tumor in adults. No effective chemotherapy regimens are available for either intraocular or metastatic uveal melanoma. Therefore, the ability of the histone deacetylase inhibitors (HDACIs), depsipeptide, sodium butyrate (NaB) and trichostatin A (TSA), to induce apoptosis and inhibit cell growth of UM cell lines in vitro was examined. METHODS: Three primary and two metastatic UM cell lines were treated in vitro with different concentrations of histone deacetylase inhibitors (HDACIs). Cell proliferation was studied in 24-well plates. Induction of apoptosis was studied by flow cytometry. Changes in gene expression of Fas/FasL, p21(Waf/Cip1), and p27(Kip1) were studied by RT-PCR. Western blot analysis was used to study histone acetylation, Fas/FasL, p21(Waf/Cip1), p27(Kip1) and caspase-3 protein levels. Real-time PCR was used to study changes in bcl-2/bax gene expression. RESULTS: A dose-dependent increase in histone acetylation was observed in all cell lines. This corresponded to significant inhibition of cell growth and induction of apoptosis in all melanoma cell lines in a concentration-dependent manner. Western blot analysis revealed dose-dependent increases in the amount of caspase-3, Fas/FasL, p21(Waf/Cip1), and p27(Kip1) proteins. However, no changes in bcl-2/bax gene expression were detected by real-time PCR. CONCLUSIONS: HDACIs are potent inhibitors of primary and metastatic UM cell growth in vitro. The apoptosis is probably mediated through the Fas/FasL signaling pathway, whereas bcl-2 appears not to be involved. These data support further clinical evaluation of depsipeptide and other HDACIs in patients with primary and metastatic UM.

Depsipeptide (FR901228) inhibits proliferation and induces apoptosis in primary and metastatic human uveal melanoma cell lines. Publishing Authors By Initials

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Depsipeptide (FR901228) inhibits proliferation and induces apoptosis in primary and metastatic human uveal melanoma cell lines. Journal Published:

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

Journal: Investigative ophthalmology & visual science

VOLUME: 44

Page Numbers: 2390-8

Journal Abbreviation: Invest. Ophthalmol. Vis. Sci.

ISSN: 0146-0404

DAY: 2

MONTH: Jun

YEAR: 2003

Depsipeptide (FR901228) inhibits proliferation and induces apoptosis in primary and metastatic human uveal melanoma cell lines. Information

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LANGUAGE: eng

NlmUniqueID: 7703701

Depsipeptide (FR901228) inhibits proliferation and induces apoptosis in primary and metastatic human uveal melanoma cell lines. Keywords Mesh Terms:

KEYWORDS: bcl-2-Associated X Protein

MESH TERMS: pathology

Chemical & Substance for Abstract: Depsipeptide (FR901228) inhibits proliferation and induces apoptosis in primary and metastatic human uveal melanoma cell lines. Information

Substance Name: Histone Deacetylases

Registry Number: EC 3.5.1.-

Grant and Affiliation Information for Depsipeptide (FR901228) inhibits proliferation and induces apoptosis in primary and metastatic human uveal melanoma cell lines.

AFFILIATION: William H Havener Eye Center, The Ohio State University, Columbus, Ohio 43210, USA. dklisovic@columbus.rr.com

Country: United States

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MEDLINETA: Invest Ophthalmol Vis Sci

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