Tamoxifen-Induced Increases in Cytoplasmic Free $ Ca^{2+} $ Levels in Human Breast Cancer Cells
Abstract Tamoxifen has been shown to increase cytoplasmic free $ Ca^{2+} $ levels [$ Ca^{2+} $]i in renal tubular cells and bladder cancer cells, and to alter $ Ca^{2+} $ signaling in MCF-7 breast cancer cells. The present study examined the effect of tamoxifen on [$ Ca^{2+} $]i in ZR-75-1 human breast cancer cells using fura-2 as an indicator. Tamoxifen increased [$ Ca^{2+} $]i at a concentration above 2 μM with an $ EC_{50} $ of 5 μM. Removing extracellular $ Ca^{2+} $ reduced the response by 48 ± 2%. In $ Ca^{2+} $-free medium, after tamoxifen-induced [$ Ca^{2+} $]i increased had returned to baseline, adding 3 mM $ Ca^{2+} $ increased [$ Ca^{2+} $]i in a concentration-dependent manner. Further, pretreatment with 10 μM tamoxifen abolished the [$ Ca^{2+} $]i increase induced by 1 μM thapsigargin (an endoplasmic reticulum $ Ca^{2+} $ pump inhibitor); and conversely, pretreatment with thapsigargin prevented tamoxifen from releasing more $ Ca^{2+} $. Tamoxifen (10 μM)-induced $ Ca^{2+} $ release was not changed by inhibiting phospholipase C activity with 2 μM U73122. Trypan blue exclusion assay revealed that tamoxifen (1–10 μM) did not alter viability after 1 min of incubation, but killed 10% of cells after 3–10 min of incubation. Together, this study shows that tamoxifen (>2 μM) induced a significant, immediate increase in [$ Ca^{2+} $]i in ZR-75-1 breast cancer cells. Tamoxifen acted by releasing $ Ca^{2+} $ from the endoplasmic reticulum $ Ca^{2+} $ stores in a manner independent of phospholipase C activity, and by inducing $ Ca^{2+} $ entry from extracellular medium. Tamoxifen may be of mild cytotoxicity after acute exposure..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2002 |
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| Erschienen: |
2002 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:71 |
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| Enthalten in: |
Breast cancer research and treatment - 71(2002), 2 vom: Jan., Seite 125-131 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chang, Hong-Tai [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| BKL: |
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| Anmerkungen: |
© Kluwer Academic Publishers 2002 |
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| doi: |
10.1023/A:1013807731642 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
OLC2045942449 |
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| 520 | |a Abstract Tamoxifen has been shown to increase cytoplasmic free $ Ca^{2+} $ levels [$ Ca^{2+} $]i in renal tubular cells and bladder cancer cells, and to alter $ Ca^{2+} $ signaling in MCF-7 breast cancer cells. The present study examined the effect of tamoxifen on [$ Ca^{2+} $]i in ZR-75-1 human breast cancer cells using fura-2 as an indicator. Tamoxifen increased [$ Ca^{2+} $]i at a concentration above 2 μM with an $ EC_{50} $ of 5 μM. Removing extracellular $ Ca^{2+} $ reduced the response by 48 ± 2%. In $ Ca^{2+} $-free medium, after tamoxifen-induced [$ Ca^{2+} $]i increased had returned to baseline, adding 3 mM $ Ca^{2+} $ increased [$ Ca^{2+} $]i in a concentration-dependent manner. Further, pretreatment with 10 μM tamoxifen abolished the [$ Ca^{2+} $]i increase induced by 1 μM thapsigargin (an endoplasmic reticulum $ Ca^{2+} $ pump inhibitor); and conversely, pretreatment with thapsigargin prevented tamoxifen from releasing more $ Ca^{2+} $. Tamoxifen (10 μM)-induced $ Ca^{2+} $ release was not changed by inhibiting phospholipase C activity with 2 μM U73122. Trypan blue exclusion assay revealed that tamoxifen (1–10 μM) did not alter viability after 1 min of incubation, but killed 10% of cells after 3–10 min of incubation. Together, this study shows that tamoxifen (>2 μM) induced a significant, immediate increase in [$ Ca^{2+} $]i in ZR-75-1 breast cancer cells. Tamoxifen acted by releasing $ Ca^{2+} $ from the endoplasmic reticulum $ Ca^{2+} $ stores in a manner independent of phospholipase C activity, and by inducing $ Ca^{2+} $ entry from extracellular medium. Tamoxifen may be of mild cytotoxicity after acute exposure. | ||
| 700 | 1 | |a Huang, Jong-Khing |4 aut | |
| 700 | 1 | |a Wang, Jue-Long |4 aut | |
| 700 | 1 | |a Cheng, Jin-Shiung |4 aut | |
| 700 | 1 | |a Lee, Kam-Chung |4 aut | |
| 700 | 1 | |a Lo, Yuk-Keung |4 aut | |
| 700 | 1 | |a Liu, Chun-Pin |4 aut | |
| 700 | 1 | |a Chou, Kang-Ju |4 aut | |
| 700 | 1 | |a Chen, Wei-Chung |4 aut | |
| 700 | 1 | |a Su, Warren |4 aut | |
| 700 | 1 | |a Law, Yee-Ping |4 aut | |
| 700 | 1 | |a Jan, Chung-Ren |4 aut | |
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