Abstract
Epidemiological studies revealed that amount of consumption of soy was inversely related to incidence of breast cancer. Genistein, the predominant isoflavone in soy, has been reported to reduce the incidence of breast cancer in animal models. To investigate whether genistein has a therapeutic effect on BRCA1-associated breast cancer, we treated Brca1 mutant mammary tumor cells with genistein. We showed that genistein treatment depleted the G1 population of cells, which was accompanied by an accumulation of cells at G2. Some genistein-treated cells entered mitosis; however, they exhibited chromosome abnormalities and maintained tetraploidy owing to abortive mitotic exit. A fraction of G2 cells underwent endoreduplication and became polyploid, which was accompanied by increased cell death through activating DNA damage response. Furthermore, our data indicated that Brca1 mutant cells were more sensitive to genistein than some other types of cancer cells, highlighting a good therapeutic potential of genistein for BRCA1-associated breast cancer.
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Abbreviations
- BRCA1:
-
breast cancer-associated gene-1
- Cdk:
-
cell cycle-dependent kinase
- DSBs:
-
double-strand breaks
- γH2AX:
-
phosphorylated form of H2AX
- MTT assay:
-
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay
- PI:
-
propidium iodide
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Acknowledgements
We thank Jesoph De Soto for a critical reading of this manuscript and all members of Deng's laboratory for technical assistance and advice. This research was supported by the Intramural Research Program of the National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, USA.
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Tominaga, Y., Wang, A., Wang, RH. et al. Genistein inhibits Brca1 mutant tumor growth through activation of DNA damage checkpoints, cell cycle arrest, and mitotic catastrophe. Cell Death Differ 14, 472–479 (2007). https://doi.org/10.1038/sj.cdd.4402037
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DOI: https://doi.org/10.1038/sj.cdd.4402037
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