Abstract
In malignant melanoma active movement of cancer cells is considered to be essential for tissue invasion. Various mechanisms, such as the Ca(2+)-calmodulin-proteinkinase C cascade or G-protein-dependent processes are considered to play a role in tumor cell functions. The assay of directional migration, combined with computer-assisted image analysis, was used to evaluate the antimigratory efficacy of drugs interfering with different steps of signal transduction pathways. Treatment with different compounds showed a more or less concentration-dependent reduction of migration rates: The Ca(2+)-channel blockers verapamil and devapamil showed a slight reduction of motility. The effect was more pronounced when the calmodulin antagonist flunarizine was used or the proteinkinase C inhibitors dequalinium, tamoxifen and H-7 were applied. A marked inhibition of motility was found with the G-protein antagonist L 651582. Thus, our results indicate that different signal transduction pathways are involved in the regulation of directional migration of K1735-M2 melanoma cells.
MeSH terms
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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Aminoimidazole Carboxamide / analogs & derivatives
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Aminoimidazole Carboxamide / pharmacology
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Animals
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Calcium Channel Blockers / pharmacology
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Cell Division / drug effects
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Cell Movement / drug effects
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Cell Movement / physiology
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Dequalinium / pharmacology
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Flunarizine / pharmacology
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GTP-Binding Proteins / antagonists & inhibitors
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Isoquinolines / pharmacology
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Melanoma, Experimental / pathology
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Melanoma, Experimental / physiopathology*
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Mice
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Piperazines / pharmacology
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Protein Kinase C / antagonists & inhibitors
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Tamoxifen / pharmacology
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Triazoles*
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / pathology
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Tumor Cells, Cultured / physiology
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Verapamil / analogs & derivatives
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Verapamil / pharmacology
Substances
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Calcium Channel Blockers
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Isoquinolines
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Piperazines
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Triazoles
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Tamoxifen
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Aminoimidazole Carboxamide
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carboxyamido-triazole
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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Verapamil
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Dequalinium
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Protein Kinase C
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GTP-Binding Proteins
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devapamil
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Flunarizine