|Methylselenol generated from selenomethionine by methioninase downregulates integrin expression and induces caspase-mediated apoptosis of B16F10 melanoma cells.|
|PMID: 17348006 Owner: NLM Status: MEDLINE|
|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.|
|Aeyung Kim; Jang-Hee Oh; Jong-Min Park; An-Sik Chung|
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|Type: Journal Article; Research Support, Non-U.S. Gov't|
|Title: Journal of cellular physiology Volume: 212 ISSN: 0021-9541 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2007 Aug|
|Created Date: 2007-06-04 Completed Date: 2007-08-16 Revised Date: 2012-06-05|
Medline Journal Info:
|Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States|
|Languages: eng Pagination: 386-400 Citation Subset: IM|
|Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.|
|APA/MLA Format Download EndNote Download BibTex|
Antineoplastic Agents / metabolism*, pharmacology
Apoptosis* / drug effects
Carbon-Sulfur Lyases / metabolism*, pharmacology
Caspases / antagonists & inhibitors, metabolism*
Dose-Response Relationship, Drug
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
Organometallic Compounds / metabolism*
Protein Kinase C-delta / antagonists & inhibitors, metabolism
Proto-Oncogene Proteins c-akt / metabolism
Selenomethionine / metabolism*, pharmacology
Skin Neoplasms / enzymology, metabolism*, pathology
Sodium Selenite / pharmacology
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors, metabolism
|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 22.214.171.124/Focal Adhesion Kinase 1; EC 126.96.36.199/Ptk2 protein, mouse; EC 188.8.131.52/Proto-Oncogene Proteins c-akt; EC 184.108.40.206/Protein Kinase C-delta; EC 220.127.116.11/p38 Mitogen-Activated Protein Kinases; EC 3.4.22.-/Caspases; EC 4.4.-/Carbon-Sulfur Lyases; EC 18.104.22.168/L-methionine gamma-lyase|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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