Tamoxifen-induced Ca2+ mobilization in bladder female transitional carcinoma cells

Citation
Ht. Chang et al., Tamoxifen-induced Ca2+ mobilization in bladder female transitional carcinoma cells, ARCH TOXIC, 75(3), 2001, pp. 184-188
Citations number
20
Categorie Soggetti
Pharmacology & Toxicology
Journal title
ARCHIVES OF TOXICOLOGY
ISSN journal
03405761 → ACNP
Volume
75
Issue
3
Year of publication
2001
Pages
184 - 188
Database
ISI
SICI code
0340-5761(200105)75:3<184:TCMIBF>2.0.ZU;2-W
Abstract
This study examined the effect of tamoxifen, an anti-breast cancer drug, on Ca2+ handling in bladder female transitional cancer cells. Changes in cyto solic free Ca2+ levels were recorded by using the Ca2+-sensitive dye fura-2 . In a dose-dependent manner, tamoxifen induced intracellular free Ca2+ con centrations ([Ca2+](i)) increases between 5 and 20 muM with an EC50 of 10 m uM. External Ca2+ removal reduced the response by 60+/-6%. Addition of 3 mM Ca2+ caused a [Ca2+](i) increase after pretreatment with 10 muM tamoxifen in Ca2+-free medium. In Ca2+-free medium, pretreatment with 10 muM tamoxife n abolished the [Ca2+](i) increase induced by 1 muM thapsigargin, an endopl asmic reticulum Ca2+ pump inhibitor. Conversely, pretreatment with 1 muM th apsigargin prevented tamoxifen from releasing more Ca2+. Inhibition of phos pholipase C-dependent inositol 1,4,5-tris-phosphate formation with 2 muM U7 3122 did not alter 10 muM tamoxifen-induced Ca2+ release. The [Ca2+](i) inc rease induced by 5 muM tamoxifen was not altered by 10 muM La3+, nifedipine , verapamil, and diltiazem. Collectively, it was found that tamoxifen incre ased [Ca2+](i) in bladder cancer cells by releasing Ca2+ from the endoplasm ic reticulum Ca2+ stores in a manner independent of phospholipase C activit y, and by inducing Ca2+ entry from external medium.