| Efficacy on anaplastic thyroid carcinoma of valproic acid alone or in combination with doxorubicin, a synthetic chenodeoxycholic acid derivative, or lactacystin. | |
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MedLine Citation:
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PMID: 19360347 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The present study investigated the mechanism underlying the antitumor activity of the histone deacetylases inhibitor valproic acid (VPA), alone and in combination with doxorubicin, a synthetic chenodeoxycholic acid derivative (HS-1200), or the proteasome inhibitor lactacystin on cultured anaplastic thyroid carcinoma KAT-18 cells. Cell viability was evaluated by trypan-blue exclusion. Western blotting determined caspase and histone deacetylase activities and expression of poly(ADP)-ribose polymerase. Induction of apoptosis was identified by Hoechst staining, DNA electrophoresis, DNA hypoploidy and cell cycle phase analysis, and measurement of mitochondrial membrane potential. Subcellular translocation of apoptosis inducing factor and caspase-activated DNase after treatment was determined by confocal microscopy following immunofluorescent staining. VPA treatment increased apoptotic death of KAT-18 cells. VPA treatment was also associated with degradation of procaspase-3, procaspase-7, and poly(ADP)-ribose polymerase; induction of histone hyperacetylation; condensation of peripheral chromatin; decreased mitochondrial membrane potential and DNA content; and decreased translocation of apoptosis inducing factor and caspase-activated DNase. VPA in combination with doxorubicin, HS-1200, or lactacystin, applied at the highest concentrations that did not induce KAT-18 cell death, efficiently induced apoptosis in KAT-18 cells. The results suggest VPA combination therapy may represent an alternative therapeutic strategy for anaplastic thyroid carcinoma. |
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Authors:
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Tae Hyun Kim; Young Hyun Yoo; Do-Young Kang; Hongsuk Suh; Moon Ki Park; Ki-Jae Park; Sung-Heun Kim |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of oncology Volume: 34 ISSN: 1019-6439 ISO Abbreviation: Int. J. Oncol. Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-04-10 Completed Date: 2009-08-03 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9306042 Medline TA: Int J Oncol Country: Greece |
Other Details:
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Languages: eng Pagination: 1353-62 Citation Subset: IM |
Affiliation:
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Department of Anatomy and Cell Biology, Dong-A University College of Medicine, Busan 602-714, Korea. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcysteine
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administration & dosage,
analogs & derivatives* Antineoplastic Combined Chemotherapy Protocols / therapeutic use* Apoptosis / drug effects Carcinoma / drug therapy* Cell Survival / drug effects Chenodeoxycholic Acid / analogs & derivatives*, chemical synthesis Dose-Response Relationship, Drug Doxorubicin / administration & dosage* Drug Evaluation, Preclinical Histone Deacetylase Inhibitors Histone Deacetylases / metabolism Humans Mitochondria / drug effects, physiology Thyroid Neoplasms / drug therapy* Treatment Outcome Tumor Cells, Cultured Valproic Acid / administration & dosage*, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Histone Deacetylase Inhibitors; 133343-34-7/lactacystin; 23214-92-8/Doxorubicin; 474-25-9/Chenodeoxycholic Acid; 616-91-1/Acetylcysteine; 99-66-1/Valproic Acid; EC 3.5.1.98/Histone Deacetylases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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