Inhibition of melanoma cell directional migration in vitro via different cellular targets.
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.
Fink-Puches
R
R
Department of Dermatology and Venerology, University of Graz, Austria.
Helige
C
C
Kerl
H
H
Smolle
J
J
Tritthart
H A
HA
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003868:Dequalinium / Q000494:pharmacology; D005444:Flunarizine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors; D007546:Isoquinolines / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology; D014230:Triazoles; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D014700:Verapamil / Q000031:analogs & derivatives / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007546:Isoquinolines; D010879:Piperazines; D014230:Triazoles; D013629:Tamoxifen; D000620:Aminoimidazole Carboxamide; C062058:carboxyamido-triazole; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D014700:Verapamil; D003868:Dequalinium; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; C055885:devapamil; D005444:Flunarizine