Abstract.
This study examined the effect of tamoxifen, an anti-breast cancer drug, on Ca2+ handling in bladder female transitional cancer cells. Changes in cytosolic free Ca2+ levels were recorded by using the Ca2+-sensitive dye fura-2. In a dose-dependent manner, tamoxifen induced intracellular free Ca2+ concentrations ([Ca2+]i) increases between 5 and 20 µM with an EC50 of 10 µM. External Ca2+ removal reduced the response by 60±6%. Addition of 3 mM Ca2+ caused a [Ca2+]i increase after pretreatment with 10 µM tamoxifen in Ca2+-free medium. In Ca2+-free medium, pretreatment with 10 µM tamoxifen abolished the [Ca2+]i increase induced by 1 µM thapsigargin, an endoplasmic reticulum Ca2+ pump inhibitor. Conversely, pretreatment with 1 µM thapsigargin prevented tamoxifen from releasing more Ca2+. Inhibition of phospholipase C-dependent inositol 1,4,5-tris-phosphate formation with 2 µM U73122 did not alter 10 µM tamoxifen-induced Ca2+ release. The [Ca2+]i increase induced by 5 µM tamoxifen was not altered by 10 µM La3+, nifedipine, verapamil, and diltiazem. Collectively, it was found that tamoxifen increased [Ca2+]i in bladder cancer cells by releasing Ca2+ from the endoplasmic reticulum Ca2+ stores in a manner independent of phospholipase C activity, and by inducing Ca2+ entry from external medium.
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Chang, HT., Huang, JK., Wang, JL. et al. Tamoxifen-induced Ca2+ mobilization in bladder female transitional carcinoma cells. Arch Toxicol 75, 184–188 (2001). https://doi.org/10.1007/s002040100212
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DOI: https://doi.org/10.1007/s002040100212