Sulforaphane inhibits growth of phenotypically different breast cancer cells
Autor: | Jedrzej Antosiewicz, Anna Herman-Antosiewicz, Angelika Kaczyńska, Anna Pawlik, Aleksandra Wiczk |
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Rok vydání: | 2013 |
Předmět: |
Cell Survival
Medicine (miscellaneous) Estrogen receptor Breast Neoplasms Biology chemistry.chemical_compound Breast cancer Microscopy Electron Transmission PI3K-AktmTOR-S6K1 pathway Isothiocyanates Cell Line Tumor Autophagy medicine Humans PTEN Phosphorylation Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Nutrition and Dietetics Cell growth PTEN Phosphohydrolase Ribosomal Protein S6 Kinases 70-kDa Original Contribution medicine.disease Phenotype chemistry Sulfoxides MCF-7 Cells Cancer research biology.protein Female Signal transduction Proto-Oncogene Proteins c-akt Sulforaphane Signal Transduction |
Zdroj: | European Journal of Nutrition |
ISSN: | 1436-6215 1436-6207 |
Popis: | Purpose Cancer development and resistance to chemotherapy correlates with aberrant activity of mitogenic pathways. In breast cancers, pro-survival PI3K-AktmTOR-S6K1 signaling pathway is often hyperactive due to overexpression of genes coding for growth factors or estrogen receptors, constitutive activation of PI3K or Akt and loss of PTEN, a negative regulator of the pathway. Since epidemiologic as well as rodent tumor studies indicate that sulforaphane (SFN), a constituent of many edible cruciferous vegetables, might be a potent inhibitor of mammary carcinogenesis, we analyzed the response of four breast cancer cell lines representing different abnormalities in ErbB2/ER-PI3K-AktmTOR-S6K1 signaling pathway to this compound. Methods Four different breast cancer cell lines were used: MDA MB 231, MCF-7, SKBR-3 and MDA MB 468. Cell viability and ultrastructure, protein synthesis, autophagy induction and phosphorylation status of Akt and S6K1 kinases upon SFN treatment were determined. Results We observed that all four cell lines are similarly sensitive to SFN. SFN decreased phosphorylation of Akt and S6K1 kinases and at higher concentrations induced autophagy in all studied cell lines. Moreover, global protein synthesis was inhibited by SFN in investigated cell lines in a dose-dependent manner. Conclusion These results indicate that SFN is a potent inhibitor of the viability of breast cancer cells representing different activity of the ErbB2/ER-PI3K-AktmTOR-S6K1 pro-survival pathway and suggest that it targets downstream elements of the pathway. |
Databáze: | OpenAIRE |
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