Hsing-Yu Chen, from the University of Rochester Medical School in New York, and colleagues examined the impact of exposure to tamoxifen on CNS cell populations.The researchers found that, in vitro, tamoxifen was cytotoxic for various CNS cell populations, and it was associated with increased cell death in the corpus callosum. In addition, tamoxifen was associated with reduced cell division in the mouse subventricular zone, the hippocampal dentate gyrus, and the corpus callosum. In vitro, MEK1/2 inhibition selectively rescued primary glial progenitors from tamoxifen cytotoxicity, while simultaneously enhancing the effect of tamoxifen on MCF7 luminal human breast cancer cells. In systematically treated mice, in vivo MEK1/2 inhibition prevented tamoxifen-induced cell death.
"Our results demonstrate unexpected cytotoxicity of this putatively benign anti-hormonal agent and offer a potential strategy for rescuing CNS cells from adverse effects of tamoxifen," the authors write.Abstract