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Carcinogenesis Advance Access published online on June 15, 2006
Carcinogenesis, doi:10.1093/carcin/bgl106
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received December 19, 2005
Revised May 23, 2006
Accepted May 26, 2006

CANCER BIOLOGY

Genistein and quercetin increase connexin43 and suppress growth of breast cancer cells

Chris M. J. Conklin 1, John F. Bechberger 1, Derek McFabe 2, Najla Guthrie 3, Elzbieta M. Kurowska 3, and Christian C. Naus 1 *

1 Department of Cellular & Physiological Sciences, University of British Columbia, Vancouver, BC, Canada
2 Depts. of Psychology (Neuroscience) & Psychiatry (Division of Developmental Disabilities) University of Western Ontario, London, Ontario, Canada, N6A 5C2
3 KGK Synergize Inc. Ste 1030, Queens Ave. London ON Canada

* To whom correspondence should be addressed.
Christian C. Naus, E-mail: conklin{at}interchange.ubc.ca


  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 to nontumorigenic cells. The purpose of this study was to determine if 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 µg/ml, 5 µg/ml) and genistein (0.5 µg/ml, 2.5 µg/ml, 15 µg/ml) upregulated Cx43 but failed to increase GJIC. Cx43 localized to the plasma membrane following genistein treatment (2.5 µg/ml, 15 µg/ml). In contrast, Cx43 aggregated in the perinuclear region following quercetin treatment (0.5 µg/ml, 2.5 µg/ml, 5 µg/ml, 15 µg/ml). Both genistein (15 µg/ml) and quercetin (2.5 µg/ml, 5 µg/ml, 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.


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