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KMID : 0379520050210010077
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한국독성학회지
2005 Volume.21 No. 1 p.77 ~ p.85
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Cadmium Induces Cell Cycle Arrest and Change in Expression of Cell Cycle Related Proteins in Breast Cancer Cell Lines
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Lee Young-Joo
Kang Tae-Seok
Kim Tae-Sung
Moon Hyun-Ju
Kang Il-Hyun
Oh Ji-Young
Kwon Hoon-Jeong
Han Soon-Young
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Abstract
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Cadmium is an environmental pollutant exposed from contaminated foods or cigarette smoking and known to cause oxidative damage in organs. We investigated the cadmium-induced apoptosis and cell arrest in human breast cancer cells, MCF-7 cells and MDA-MB-231 cells. Obvious apoptotic cell death was shown in CdCl₂ 100 μM treatment for 12 hr, which were determined by DAPI staining and flow cytometric analysis. In cell cycle analysis, MCF-7 cells and MDA-MB-231 cells were arrested in S phase and G2/M phase respectively. These could be explained by the induction of cell cycle inhibitory protein, p21/sup Waf1/Cip1/ and p27/sup Kip1/, expression and reduction of cyclin/Cdk complexes in both cell lines. The decreased expression of cyclin A and Cdk2 in MCF-7 cells and cyclin B1 and Cdc2 in MDA-MB-231 cells were consistent with the flow cytometric observation. p-ERK expression was increased dose-dependent manner in both cell lines. It suggests that ERK MAPK pathway are involved in cadmium-induced cell cycle arrest and apoptosis. Moreover, cotreatment of zinc (100 μM, 12 hr) recovered the cadmium-induced cell arrest in both cells, which shows cadmium-induced oxidative stress mediates apoptosis and cell cycle arrest in human breast cancer cells.
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KEYWORD
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Cadmium, Cell cycle arrest, Cell cycle regulatory protein, ERK, Antioxidant, Zinc
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