title: Sulforaphane inhibits growth of phenotypically different breast cancer cells.
abstract: OBJECTIVE
  Cancer development and resistance to chemotherapy correlates with aberrant activity of mitogenic pathways. In breast cancers, pro-survival PI3K-Akt-mTOR-S6K1 [corrected] 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-Akt-mTOR-S6K1[corrected] 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.
  
  
  CONCLUSIONS
  These results indicate that SFN is a potent inhibitor of the viability of breast cancer cells representing different activity of the ErbB2/ER-PI3K-Akt-mTOR-S6K1 [corrected] pro-survival pathway and suggest that it targets downstream elements of the pathway.
authors: Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308, Gdańsk, Poland.
authors: Anna
authors: A
authors: Pawlik
authors: Aleksandra
authors: A
authors: Wiczk
authors: Angelika
authors: A
authors: Kaczyńska
authors: Jędrzej
authors: J
authors: Antosiewicz
authors: Anna
authors: A
authors: Herman-Antosiewicz
mesh_terms: D001343:Autophagy / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D061986:MCF-7 Cells / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013454:Sulfoxides
chemical_list: D017879:Isothiocyanates; D013454:Sulfoxides; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C016766:sulforaphane
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