| Methylselenol generated from selenomethionine by methioninase downregulates integrin expression and induces caspase-mediated apoptosis of B16F10 melanoma cells. | |
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MedLine Citation:
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PMID: 17348006 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Melanoma is a highly metastatic cancer resistant to current chemotherapeutic and radiotherapeutic approaches. Several studies have shown that interactions between cancer cells and the extracellular matrix (ECM) are critical for the survival and invasion of metastatic cancer cells. In this study, we examine the effects of methylselenol generated from selenomethionine (SeMet) by methioninase (METase) on cell proliferation, adhesion, and expression of integrins in murine melanoma B16F10 cells, which are metastatic in the lungs of syngeneic C57BL/6J mice. Combined treatment with SeMet-METase decreased the expression of integrins alpha(4), beta(1), alpha(nu), and beta(3), and inhibited melanoma-ECM adhesion. Caspase-mediated apoptosis was induced following loss of cell adherence. Phosphorylation of focal adhesion kinase (FAK) and Akt, related to integrin-mediated survival, were decreased upon treatment with SeMet-METase while phosphorylation of p38, PKC-delta, and IkappaBalpha increased. In the presence of specific inhibitors of p38, PKC-delta, and NF-kappaB, expression of integrins and cell adhesion to ECM were maintained and cell apoptosis was prevented in SeMet-METase-treated melanoma cells. Treatment with caspase inhibitors restored cell viability and blocked poly (ADP-ribose) polymerase (PARP) cleavage, but did not restore integrin expression and cell adhesion to ECMs reduced by SeMet-METase. Based on these results, we propose that combined treatment with SeMet-METase induces caspase-mediated apoptosis in melanoma cells by altering integrin expression and adhesion. Furthermore, activation of p38, PKC-delta, and NF-kappaB is a prerequisite for the down-regulation of integrin expression, followed by detachment-mediated apoptosis. |
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Authors:
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Aeyung Kim; Jang-Hee Oh; Jong-Min Park; An-Sik Chung |
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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: Journal of cellular physiology Volume: 212 ISSN: 0021-9541 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2007 Aug |
Date Detail:
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Created Date: 2007-06-04 Completed Date: 2007-08-16 Revised Date: 2012-06-05 |
Medline Journal Info:
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Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 386-400 Citation Subset: IM |
Affiliation:
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Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents / metabolism*, pharmacology Apoptosis* / drug effects Carbon-Sulfur Lyases / metabolism*, pharmacology Caspases / antagonists & inhibitors, metabolism* Cell Adhesion Cell Cycle Cell Proliferation Cell Shape Cell Survival Dose-Response Relationship, Drug Down-Regulation Enzyme Inhibitors / pharmacology Extracellular Matrix / metabolism Focal Adhesion Kinase 1 / metabolism I-kappa B Proteins / metabolism Integrins / metabolism* Melanoma, Experimental / enzymology, metabolism*, pathology Methanol / analogs & derivatives Mice Organometallic Compounds / metabolism* Organoselenium Compounds Phosphorylation Protein Kinase C-delta / antagonists & inhibitors, metabolism Proto-Oncogene Proteins c-akt / metabolism Selenomethionine / metabolism*, pharmacology Signal Transduction Skin Neoplasms / enzymology, metabolism*, pathology Sodium Selenite / pharmacology p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Enzyme Inhibitors; 0/I-kappa B Proteins; 0/Integrins; 0/Organometallic Compounds; 0/Organoselenium Compounds; 10102-18-8/Sodium Selenite; 1464-42-2/Selenomethionine; 60343-91-1/methaneselenol; 67-56-1/Methanol; EC 2.7.10.1/Focal Adhesion Kinase 1; EC 2.7.10.2/Ptk2 protein, mouse; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.13/Protein Kinase C-delta; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.4.22.-/Caspases; EC 4.4.-/Carbon-Sulfur Lyases; EC 4.4.1.11/L-methionine gamma-lyase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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