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.