Tamoxifen-induced Ca2+ mobilization in bladder female transitional carcinoma cells.
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 microM with an EC50 of 10 microM. External Ca2+ removal reduced the response by 60+/-6%. Addition of 3 mM Ca2+ caused a [Ca2+]i increase after pretreatment with 10 microM tamoxifen in Ca2+-free medium. In Ca2+-free medium, pretreatment with 10 microM tamoxifen abolished the [Ca2+]i increase induced by 1 microM thapsigargin, an endoplasmic reticulum Ca2+ pump inhibitor. Conversely, pretreatment with 1 microM thapsigargin prevented tamoxifen from releasing more Ca2+. Inhibition of phospholipase C-dependent inositol 1,4,5-tris-phosphate formation with 2 microM U73122 did not alter 10 microM tamoxifen-induced Ca2+ release. The [Ca2+]i increase induced by 5 microM tamoxifen was not altered by 10 microM 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.
Chang
H T
HT
Department of Surgery, Kaohsiung Veterans General Hospital, Taiwan.
Huang
J K
JK
Wang
J L
JL
Cheng
J S
JS
Lee
K C
KC
Lo
Y K
YK
Lin
M C
MC
Tang
K Y
KY
Jan
C R
CR
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D006801:Humans; D011760:Pyrrolidinones / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
D016588:Anticarcinogenic Agents; D004791:Enzyme Inhibitors; D004963:Estrenes; D005456:Fluorescent Dyes; D011760:Pyrrolidinones; D013629:Tamoxifen; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D019284:Thapsigargin; D010738:Type C Phospholipases; D016257:Fura-2