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Tamoxifen blocks both proliferation and voltage-dependent K+ channels of neuroblastoma cells
B Rouzaire-Dubois1, J M Dubois
1Laboratoire de Physiologie Comparée, URA CNRS 1121, Université Paris-Sud, Orsay, France.
Abstract:
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.
Insights
Tamoxifen (TAM) inhibits neuroblastoma cell proliferation and affects potassium (K+) channels. This suggests TAM
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Tamoxifen (TAM) is a widely used drug with known effects on cell proliferation.
- Voltage-dependent potassium (K+) channels play crucial roles in cellular functions, including cell division.
Purpose of the Study:
- To investigate the impact of tamoxifen on cell proliferation and voltage-dependent K+ channels in mouse neuroblastoma cells (NG 108-15).
- To explore the potential link between tamoxifen's effects on K+ channels and its antitumour activity.
Main Methods:
- Utilized mouse neuroblastoma cells (NG 108-15) for experimental studies.
- Assessed cell proliferation inhibition and cytotoxicity using varying concentrations of tamoxifen.
- Electrophysiological recordings were performed to analyze whole-cell K+ currents and K+ conductance-voltage relationships.
Main Results:
- Tamoxifen inhibited cell proliferation with an ED50 of 2 microM and exhibited cytotoxicity at concentrations of 2.5 microM and above.
- Tamoxifen accelerated K+ current inactivation (apparent dissociation constant of 0.46 microM) and shifted the K+ conductance-voltage curve negatively (apparent dissociation constant of 1.07 microM).
- A significant correlation was observed between tamoxifen's inhibition of cell proliferation and its reduction of resting K+ flux.
Conclusions:
- The findings suggest that K+ channel function is involved in the control of cell mitosis.
- Tamoxifen's antitumour effects may be attributed to its interaction with and modulation of K+ channels.