Document Detail


Inhibition of calcineurin by cyclosporine A exerts multiple effects on human melanoma cell lines HT168 and WM35.
MedLine Citation:
PMID:  19287956     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The immunosuppressant cyclosporine A (CsA) is a specific pharmacological inhibitor of calcineurin, the Ca2+-calmodulin activated phospho-Ser/Thr-specific protein phosphatase. Although calcineurin-inhibiting compounds are applied for local treatment of psoriasis or atopic dermatitis in dermatological practice, little is known about the functions of calcineurin in epidermis-derived malignancies. We investigated the effects of CsA on two human melanoma cell lines, the metastasis forming HT168 and WM35 established from an RGP primary lesion. CsA of 2 microM lowered the enzyme activity by 50% and caused elevation in both mRNA and protein expression of calcineurin. Cell proliferation was diminished, as well as the cellular morphology and the actin organization were altered in both cell lines. CsA increased cell death moderately in both cell lines and reduced the metabolic activity of HT168 cells, but not that of WM35 cells. CsA also elevated the expressions of both Bcl-2 and ERK1/2. Fibronectin guided migration of HT168 cells was stimulated under the effect of CsA, while that of WM35 cells was reduced, moreover, HT168 cells switched from the expression of beta3 to beta1 integrin, but WM35 cells continued to express beta3. Based on our results we propose a multiple, partly malignancy-dependent role of calcineurin in these melanoma cell lines.
Authors:
Tamás Juhász; Csaba Matta; Gábor Veress; Georgina Nagy; Zsolt Szíjgyártó; Zsanett Molnár; János Fodor; Róza Zákány; Pál Gergely
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of oncology     Volume:  34     ISSN:  1019-6439     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-16     Completed Date:  2009-07-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  995-1003     Citation Subset:  IM    
Affiliation:
Department of Anatomy, Histology and Embryology, Medical and Health Science Centre, University of Debrecen, Hungary.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis
Calcineurin / antagonists & inhibitors*
Calcium / chemistry,  metabolism
Calmodulin / chemistry
Cell Line, Tumor
Cell Proliferation
Cyclosporine / pharmacology*
Cytosol / metabolism
Flow Cytometry
Gene Expression Regulation, Neoplastic*
Humans
Immunohistochemistry
Melanoma / drug therapy*,  metabolism*
Psoriasis / metabolism
RNA, Messenger / metabolism
Chemical
Reg. No./Substance:
0/Calmodulin; 0/RNA, Messenger; 59865-13-3/Cyclosporine; 7440-70-2/Calcium; EC 3.1.3.16/Calcineurin

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