Effects of a calcium-antagonist (flunarizine) on the in vitro growth of B16 mouse melanoma cells.
Flunarizine, a drug which binds to calmodulin, was found to inhibit both the growth rate and the survival fraction of a B16 mouse melanoma cell line cultured in vitro. Both of these effects, that are dose and time-dependent, occurred at doses which in vitro cause a 50% inhibition of the calmodulin-activated cyclic nucleotide phosphodiesterase prepared from the tumor. Cyclic AMP was increased in treated B16 melanoma cells, while DNA synthesis was inhibited, though the DNA content/cell was increased. The possible mechanisms of the drug's action are discussed herein.
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002460:Cell Line; D002936:Cinnarizine / Q000031:analogs & derivatives / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005444:Flunarizine; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009712:Nucleotides, Cyclic / Q000032:analysis; D010879:Piperazines / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D004273:DNA, Neoplasm; D009712:Nucleotides, Cyclic; D010879:Piperazines; D002936:Cinnarizine; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D005444:Flunarizine