Tamoxifen blocks both proliferation and voltage-dependent K+ channels of neuroblastoma cells.
The effects of tamoxifen (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 microM and was cytotoxic from and beyond 2.5 microM. TAM accelerated the apparent inactivation of the whole cell K+ current with an apparent dissociation constant of 0.46 microM, and shifted the peak K+ conductance-voltage curve towards negative voltages with an apparent dissociation constant of 1.07 microM. 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 resting K+ flux. The results suggest that cell mitosis is, in some way, controlled by the functioning of K+ channels and that the antitumour action of tamoxifen could be due to its interaction with K+ channels.
Rouzaire-Dubois
B
B
Laboratoire de Physiologie Comparée, URA CNRS 1121, Université Paris-Sud, Orsay, France.
Dubois
J M
JM
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004553:Electric Conductivity; D004594:Electrophysiology; D008564:Membrane Potentials / Q000187:drug effects; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D015221:Potassium Channels; D013629:Tamoxifen; D012964:Sodium; D011188:Potassium