flunarizine and carboxyamido-triazole

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.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Aminoimidazole Carboxamide; Animals; Calcium Channel Blockers; Cell Division; Cell Movement; Dequalinium; Flunarizine; GTP-Binding Proteins; Isoquinolines; Melanoma, Experimental; Mice; Piperazines; Protein Kinase C; Signal Transduction; Tamoxifen; Triazoles; Tumor Cells, Cultured; Verapamil