Effect of diethylstilbestrol on Ca2+ handling and cell viability in human breast cancer cells |
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Authors: | Chang Hong-Tai Hsu Shu-Shong Chen Jin-Shyr Lin Ko-Long Wang Jue-Long Cheng He-Hsiung Lu Yih-Chau Jiann Bang-Ping Liu Chun-Peng Huang Jong-Khing Yeh Jeng Hsien Chiang An-Jen Chen Wei-Chuan Jan Chung-Ren |
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Institution: | Department of Surgery, Kaohsiung Veterans General Hospital Kaohsiung, Taiwan 813, Republic of China. |
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Abstract: | In human breast cancer cells, the effect of the widely prescribed estrogen diethylstilbestrol (DES) on intracellular Ca2+ concentrations (Ca2+]i) and cell viability was explored by using fura-2 and trypan blue exclusion, respectively. DES caused a rise in Ca2+]i in a concentration-dependent manner (EC50 = 15 microM). DES-induced Ca2+]i rise was reduced by 80 % by removal of extracellular Ca2+. DES-induced Mn(2+)-associated quench of intracellular fura-2 fluorescence also suggests that DES induced extracellular Ca2+ influx. In Ca(2+)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase, caused a monophasic Ca2+]i rise, after which the increasing effect of DES on Ca2+]i was greatly inhibited. Conversely, pretreatment with DES to deplete intracellular Ca2+ stores totally prevented thapsigargin from releasing more Ca2+, whereas ionomycin added afterward still released some Ca2+. These findings suggest that in human breast cancer cells, DES increases Ca2+]i by stimulating extracellular Ca2+ influx and also by causing intracellular Ca2+ release from the endoplasmic reticulum. Acute trypan blue exclusion studies suggest that 10-20 NM DES killed cells in a time-dependent manner. |
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