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dc.contributor.authorMurray, Tessa Jen_US
dc.contributor.authorYang, Xinhaien_US
dc.contributor.authorSherr, David Hen_US
dc.date.accessioned2012-01-12T16:41:37Z
dc.date.available2012-01-12T16:41:37Z
dc.date.copyright2006en_US
dc.date.issued2006-3-27en_US
dc.identifier.citationMurray, Tessa J, Xinhai Yang, David H Sherr. "Growth of a human mammary tumor cell line is blocked by galangin, a naturally occurring bioflavonoid, and is accompanied by down-regulation of cyclins D3, E, and A" Breast Cancer Research 8(2):R17. (2006)en_US
dc.identifier.issn1465-542Xen_US
dc.identifier.urihttp://hdl.handle.net/2144/3358
dc.description.abstractINTRODUCTION. This study was designed to determine if and how a non-toxic, naturally occurring bioflavonoid, galangin, affects proliferation of human mammary tumor cells. Our previous studies demonstrated that, in other cell types, galangin is a potent inhibitor of the aryl hydrocarbon receptor (AhR), an environmental carcinogen-responsive transcription factor implicated in mammary tumor initiation and growth control. Because some current breast cancer therapeutics are ineffective in estrogen receptor (ER) negative tumors and since the AhR may be involved in breast cancer proliferation, the effects of galangin on the proliferation of an ER-, AhRhigh line, Hs578T, were studied. METHODS. AhR expression and function in the presence or absence of galangin, a second AhR inhibitor, α-naphthoflavone (α-NF), an AhR agonist, indole-3-carbinol, and a transfected AhR repressor-encoding plasmid (FhAhRR) were studied in Hs578T cells by western blotting for nuclear (for instance, constitutively activated) AhR and by transfection of an AhR-driven reporter construct, pGudLuc. The effects of these agents on cell proliferation were studied by 3H-thymidine incorporation and by flow cytometry. The effects on cyclins implicated in mammary tumorigenesis were evaluated by western blotting. RESULTS. Hs578T cells were shown to express high levels of constitutively active AhR. Constitutive and environmental chemical-induced AhR activity was profoundly suppressed by galangin as was cell proliferation. However, the failure of α-NF or FhAhRR transfection to block proliferation indicated that galangin-mediated AhR inhibition was either insufficient or unrelated to its ability to significantly block cell proliferation at therapeutically relevant doses (IC50 = 11 μM). Galangin inhibited transition of cells from the G0/G1 to the S phases of cell growth, likely through the nearly total elimination of cyclin D3. Expression of cyclins A and E was also suppressed. CONCLUSION. Galangin is a strong inhibitor of Hs578T cell proliferation that likely mediates this effect through a relatively unique mechanism, suppression of cyclin D3, and not through the AhR. The results suggest that this non-toxic bioflavonoid may be useful as a chemotherapeutic, particularly in combination with agents that target other components of the tumor cell cycle and in situations where estrogen receptor-specific therapeutics are ineffective.en_US
dc.description.sponsorship(PO1 ES11624, PO1-HL68705, RO1-ES06086, P42-ES07381)en_US
dc.language.isoenen_US
dc.publisherBioMed Centralen_US
dc.rightsCopyright 2006 Murray et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_US
dc.titleGrowth of a Human Mammary Tumor Cell Line Is Blocked by Galangin, a Naturally Occurring Bioflavonoid, and Is Accompanied by Down-Regulation of Cyclins D3, E, and Aen_US
dc.typearticleen_US
dc.identifier.doi10.1186/bcr1391en_US
dc.identifier.pubmedid16569260en_US
dc.identifier.pmcid1557718en_US


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Copyright 2006 Murray et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as Copyright 2006 Murray et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.