title: Inhibition of calcineurin by cyclosporine A exerts multiple effects on human melanoma cell lines HT168 and WM35.
abstract: 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.affiliation: Department of Anatomy, Histology and Embryology, Medical and Health Science Centre, University of Debrecen, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Juhász
authors.forename: Csaba
authors.initials: C
authors.lastname: Matta
authors.forename: Gábor
authors.initials: G
authors.lastname: Veress
authors.forename: Georgina
authors.initials: G
authors.lastname: Nagy
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szíjgyártó
authors.forename: Zsanett
authors.initials: Z
authors.lastname: Molnár
authors.forename: János
authors.initials: J
authors.lastname: Fodor
authors.forename: Róza
authors.initials: R
authors.lastname: Zákány
authors.forename: Pál
authors.initials: P
authors.lastname: Gergely
mesh_terms: D017209:Apoptosis; D065095:Calcineurin Inhibitors; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002147:Calmodulin / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016572:Cyclosporine / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism*; D011565:Psoriasis / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D065095:Calcineurin Inhibitors; D002147:Calmodulin; D012333:RNA, Messenger; D016572:Cyclosporine; D002118:Calcium