title: Genistein and quercetin increase connexin43 and suppress growth of breast cancer cells.
abstract: Connexin proteins form gap junctions, which permit direct exchange of cytoplasmic contents between neighboring cells. Evidence indicates that gap junctional intercellular communication (GJIC) is important for maintaining homeostasis and preventing cell transformation. Furthermore, connexins may have independent functions including tumor growth suppression. Most tumors express less connexins, have reduced GJIC and have increased growth rates compared with non-tumorigenic cells. The purpose of this study was to determine whether common flavonoids, genistein and quercetin, increase connexin43 (Cx43) levels, improve GJIC and suppress growth of a metastatic human breast tumor cell line (MDA-MB-231). Quercetin (2.5, 5 microg/ml) and genistein (0.5, 2.5, 15 microg/ml) upregulated Cx43 but failed to increase GJIC. Cx43 localized to the plasma membrane following genistein treatment (2.5, 15 mug/ml). In contrast, Cx43 aggregated in the perinuclear region following quercetin treatment (0.5, 2.5, 5, 15 microg/ml). Both genistein (15 microg/ml) and quercetin (2.5, 5, 15 microg/ml) significantly reduced MDA-MB-231 cell proliferation. In summary, genistein and quercetin increase Cx43 and suppress MDA-MB-231 cell proliferation at physiologically relevant concentrations. These results demonstrate that genistein and quercetin are potential anti-breast cancer agents.
authors.affiliation: Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Chris M J
authors.initials: CM
authors.lastname: Conklin
authors.forename: John F
authors.initials: JF
authors.lastname: Bechberger
authors.forename: Derrick
authors.initials: D
authors.lastname: MacFabe
authors.forename: Najla
authors.initials: N
authors.lastname: Guthrie
authors.forename: Elzbieta M
authors.initials: EM
authors.lastname: Kurowska
authors.forename: Christian C
authors.initials: CC
authors.lastname: Naus
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D018031:Connexin 43 / Q000378:metabolism*; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007124:Immunoenzyme Techniques; D011794:Quercetin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D018031:Connexin 43; D011794:Quercetin; D019833:Genistein