title: Exposure of breast cancer cells to a subcytotoxic dose of apigenin causes growth inhibition, oxidative stress, and hypophosphorylation of Akt.
abstract: Epidemiological studies show that fruit- and vegetable-rich diets are associated with a reduced risk of developing certain forms of cancer, including breast cancer. In this study we demonstrate that a subcytotoxic concentration of apigenin, which is a flavone found at high concentrations in parsley, onions, grapefruit, oranges, and chamomile tea, inhibited DNA synthesis in a panel of human breast cancer cell lines (MDA-MB-231, MBA-MB-468, MCF-7, SK-BR-3). Decreased proliferation of MDA-MB-468 cells in the presence of apigenin was associated with G2/M phase cell cycle arrest and the production of reactive oxygen species. Apigenin-treated MDA-MB-468 cells also showed reduced phosphorylation of Akt (protein kinase B), which is an essential effector serine/threonine kinase in the phosphatidylinositide 3-kinase pathway that promotes tumor growth and progression. However, exposure to the antioxidant reduced glutathione failed to reverse apigenin-mediated inhibition of Akt phosphorylation and cell proliferation, indicating that these effects were not due to oxidative stress. Taken together, these findings suggest that low-dose apigenin has the potential to slow or prevent breast cancer progression.
authors.affiliation: Department of Microbiology and Immunology, Dalhousie University, PO Box 15000, Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Harrison
authors.affiliation: Department of Pathology, Dalhousie University, PO Box 15000, Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: Melanie R
authors.initials: MR
authors.lastname: Power Coombs
authors.affiliation: Department of Microbiology and Immunology, Dalhousie University, PO Box 15000, Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Delaney
authors.affiliation: Department of Microbiology and Immunology, Dalhousie University, PO Box 15000, Halifax, Nova Scotia B3H 4R2, Canada; Department of Pathology, Dalhousie University, PO Box 15000, Halifax, Nova Scotia B3H 4R2, Canada; Department of Surgery, Dalhousie University, PO Box 15000, Halifax, Nova Scotia B3H 4R2, Canada. Electronic address: d.w.hoskin@dal.ca.
authors.forename: David W
authors.initials: DW
authors.lastname: Hoskin
mesh_terms: D047310:Apigenin / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D061986:MCF-7 Cells; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
chemical_list: D047310:Apigenin; D051057:Proto-Oncogene Proteins c-akt
keywords: Apigenin; Breast cancer; Cell cycle; Flavone; Protein kinase B/Akt; Reactive oxygen species