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KMID : 0613820070170081053
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Journal of Life Science
2007 Volume.17 No. 8 p.1053 ~ p.1062
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Tamoxifen Induces Mitochondrial-dependent Apoptosis via Intracellular Ca2+ Modulation
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Jang Eun-Seong
Kim Ji-Young
Kim Byeong-Gee
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Abstract
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In the present work, we show that tamoxifen(Tam)-induced cytotoxicity is due to the mitochondrial- dependent pathway triggered by the intracellular Ca²? increase in MCF-7 human breast cancer cells. Tam induced the intracellular Ca²? increase. According to the experimental results with Ca²? channel blockers, Tam-induced Ca²? uptake seemed to depend on the voltage-sensitive Ca²? channel at the early stage, but at later stages the intracellular Ca²? increases are more likely due partly to the release of stored Ca²? and partly to the capacitative Ca²? or other entry pathways. Tam-induced Ca²? increase led to the release of cytochrome c from mitochondria into the cytosol and the change of mitochondrial membrane potential. In MCF-7 cells, caspase-7 plays a key role in the downstream of apoptosis because caspase-3 is absent. In the cells treated with Tam, caspase-7 cleavage was increased almost two-fold. There was no marked alteration in the level of anti-apoptotic Bcl-2 protein; however, the cells showed increased expression of pro-apoptotic Bax protein more than two-fold in response to Tam. These results imply that the apoptotic signaling pathway activated by Tam is likely to be mediated via the mitochondrial-dependent pathway.
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KEYWORD
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Apoptosis, calcium, cytochrome c, MCF-7, tamoxifen
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