TAMOXIFEN BLOCKS BOTH PROLIFERATION AND VOLTAGE-DEPENDENT K+ CHANNELS OF NEUROBLASTOMA-CELLS

The effects of tamoxifin (TAM) on cell proliferation and voltage-dependent K+ channels were studied on the mouse neuroblastoma cells NG 108-15. TAM inhibited cell proliferation with an effective dose inducing a half maximum effect (ED50) of 2 μM and was cytotoxic for and beyond 2.5 μM. TAM accelerated the apparent inactivation of the whole cell K+ current with an apparent dissociation constant of 0.46 μM, and shifted the peak K+ conductance-voltage curve towards negative voltages with an apparent dissociation constant of 1.07 μM. The K+ flux at the resting potential, calculated from the time integral of the K+ current recorded during depolarizations, was decreased by TAM. The effect of TAM on the cell proliferation was perfectly correlated with the effect of TAM on the restling K+ flux. The results suggest that cell mitosis is, in some way, controlleld by the functioning of K+ channels and that the antitumour action of tamoxifen could be due to its interaction with K+ channels. © 1990.