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KMID : 0382320060260010012
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Environmental Mutagens and Carcinogens
2006 Volume.26 No. 1 p.12 ~ p.19
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Study on the Estrogen Receptor Mediated Toxicity of Cadmium and Protective Effects of Antioxidant
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Kim Tae-Sung
Hong Jin-Tae
Kang Ho-Il
Han Soon-Young
Moon Hyun-Ju
Kang Tae-Seok
Kang Il-Hyun
Lee Young-Joo
Choi Eun-Hee
Hong Jin-Hwan
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Abstract
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Cadmium, a human carcinogen, can induce toxicity in various cell lines and organs. Despite extensive research, the mechanisms of cadmium-induced cell toxicity and estrogenic potential in human are not clear. This study was performed to investigate cadmium-induced toxicity on human breast cancer cells :MCF-7 cells, an estrogen receptor (ER) positive breast cancer cells, and MDA-MB-231 cells, an ER negative breast cancer cells. MCF-7 cells was proved to be more sensitive than the other cell lines (IC50 = 50 μM at MCF-7 cells and 120 μM at MDA-MB-231). The expression of JNK and AP-1 transcription factors such as c-Jun and c-Fos dependent transcription were increased by cadmium treatment. Inhibition of ER activation by ER antagonist (tamoxifen or ICI 182,780) significantly recovered the viablity and inhibited apoptotic cell death. This suggested that cadmium-induced cell death in ER (+) cells was mediated by JNK/AP-1 pathway and this pathway was more stimulated by ER activated by cadmium. Co-treatment of antioxidants such as selenium (Se), butylated hydroxyanisole (BHA), glutathione (GSH), or N-acetyl-L-cysteine (NAC) recovered the cadmium-induced cell death in MCF-7 cells. Cadmium-induced lipid peroxidation was decreased by GSH, NAC, or BHA in MCF-7 cells. The expression of SOD protein was decreased by cadmium (100 μM) but recovered by GSH, NAC, BHA, or Se. Our data showed that the cadmium-induced cell toxicity in human breast cancer cells could be protected by the antioxidants (Se, BHA, NAC, GSH, or NAC) and ER antagonist (tamoxifen or ICI 182,780). Therefore, toxicity of cadmium in breast cancer were mediated by oxidative stress and ERα.
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KEYWORD
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Cadmium, Estrogen receptors, MCF-7 cells
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