Cadmium induces reactive oxygen species-dependent apoptosis in MCF-7 human breast cancer cell line.
OBJECTIVE
Although low concentrations of cadmium exposure may enhance growth of human cultured cells, high and long term of this heavy metal leads to cell death through apoptosis or necrosis. This study was conducted to define the underlying biochemical mechanism of Cd-induced cell death in MCF-7 human breast cancer cell line.


METHODS
The MCF-7 breast cancer cells were treated with different concentrations of CdCl2 and cell viability was assessed using the MTT assay. A propidium iodide (PI) and annexin-V staining flow cytometric method was used for apoptosis detection. Hoechst 33342 staining was used to observe the morphological changes of cell apoptosis. The cellular DNA was isolated using DNA kit extraction and analyzed electrophoretically. Intracellular reactive oxygen species (ROS) levels were quantified using the fluorescent dye (DCFH-DA).


RESULTS
A progressive loss in cell viability and an increased number of apoptotic cells were observed upon 48 h exposure to CdCl2. N-acetylcysteine (NAC) administration reversed the cadmium cytotoxicity effects and protected cells from apoptotic death. Simultaneously, significant elevations of ROS levels were revealed in a dose-dependent manner during the exposure. Typical morphological changes of apoptosis were observed with Hoechst staining after cadmium treatment.


CONCLUSIONS
These results suggest that during the apoptosis mediated by cadmium chloride, ROS production and oxidative damage may be an initiating event and responsible for the mechanism of MCF-7 human breast cell death.
Department of Biochemistry and Bioinformatics Research Center, School of Pharmacy and Pharmaceutical Sciences .
Ali
A
Khojastehfar
Mahmoud
M
Aghaei
Marjan
M
Gharagozloo
Mojtaba
M
Panjehpour
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019256:Cadmium Chloride / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000975:Antioxidants; D017382:Reactive Oxygen Species; D019256:Cadmium Chloride
Apoptosis; MCF-7; ROS; breast cancer; cadmium