Carcinogenesis Advance Access originally published online on June 15, 2006
Carcinogenesis 2007 28(1):93-100; doi:10.1093/carcin/bgl106
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Genistein and quercetin increase connexin43 and suppress growth of breast cancer cells
Department of Cellular and Physiological Sciences, University of British Columbia Vancouver, BC, Canada
1 Department of Psychology (Neuroscience), University of Western Ontario London, ON, Canada N6A 5C2
2 Department of Psychiatry (Division of Developmental Disabilities), University of Western Ontario London, ON, Canada N6A 5C2
3 KGK Synergize Inc. Suite 1030, Queens Avenue, London, ON, Canada
*To whom correspondence should be addressed Email: cnaus{at}interchange.ubc.ca
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 µg/ml) and genistein (0.5, 2.5, 15 µg/ml) upregulated Cx43 but failed to increase GJIC. Cx43 localized to the plasma membrane following genistein treatment (2.5, 15 µg/ml). In contrast, Cx43 aggregated in the perinuclear region following quercetin treatment (0.5, 2.5, 5, 15 µg/ml). Both genistein (15 µg/ml) and quercetin (2.5, 5, 15 µg/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.