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Chemopreventive and therapeutic activity of dietary blueberry against estrogen-mediated breast cancer.

Jeyabalan J, Aqil F, Munagala R, Annamalai L, Vadhanam MV, Gupta RC - J. Agric. Food Chem. (2014)

Bottom Line: Berries are gaining increasing importance lately for their chemopreventive and therapeutic potential against several cancers.The effect on mammary tumorigenesis was largely due to down-regulation of CYP 1A1 and ER-α gene expression and also favorable modulation of microRNA (miR-18a and miR-34c) levels.These data suggest that the blueberry blend tested is effective in inhibiting E2-mediated mammary tumorigenesis in both preventive and therapeutic modes.

View Article: PubMed Central - PubMed

Affiliation: James Graham Brown Cancer Center, ‡Department of Medicine, and #Department of Pharmacology and Toxicology, University of Louisville , Louisville, Kentucky 40202, United States.

ABSTRACT
Berries are gaining increasing importance lately for their chemopreventive and therapeutic potential against several cancers. In earlier studies, a blueberry-supplemented diet has shown protection against 17β-estradiol (E2)-mediated mammary tumorigenesis. This study tested both preventive and therapeutic activities of diet supplemented with whole blueberry powder (50:50 blend of Tifblue and Rubel). Animals received 5% blueberry diet, either 2 weeks prior to or 12 weeks after E2 treatment in preventive and therapeutic groups, respectively. Both interventions delayed the tumor latency for palpable mammary tumors by 28 and 37 days, respectively. Tumor volume and multiplicity were also reduced significantly in both modes. The effect on mammary tumorigenesis was largely due to down-regulation of CYP 1A1 and ER-α gene expression and also favorable modulation of microRNA (miR-18a and miR-34c) levels. These data suggest that the blueberry blend tested is effective in inhibiting E2-mediated mammary tumorigenesis in both preventive and therapeutic modes.

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Related in: MedlinePlus

Presenceof epithelial dysplasia and ductular papillomas from mammarytissue of rats treated with E2 implant for 12 weeks. (A)Image of mammary section at 40× magnification showing long papillaryprojections from ductular walls (thin arrows) and ducts lined withhyperplastic epithelium with two or more layers (bold arrows). Insetshows 400× magnification of papillary projections. (B) Mammarysection at 600× magnification with nuclei showing karyomegaly,which are hyperchromatic containing one to three distinct nucleoli(thin arrows).
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fig3: Presenceof epithelial dysplasia and ductular papillomas from mammarytissue of rats treated with E2 implant for 12 weeks. (A)Image of mammary section at 40× magnification showing long papillaryprojections from ductular walls (thin arrows) and ducts lined withhyperplastic epithelium with two or more layers (bold arrows). Insetshows 400× magnification of papillary projections. (B) Mammarysection at 600× magnification with nuclei showing karyomegaly,which are hyperchromatic containing one to three distinct nucleoli(thin arrows).

Mentions: In all animals that were treated withE2 for 12 weeks (n = 21), there was expansionof mammary tissue with proliferation of terminal buds that differentiatedinto acini. The acinar epithelial cells were frequently vacuolated,and the acini contained amphophilic inspissated secretory materialfilling the lumina (Figure 3A). Concomitantly,there was proliferation of ductules and ducts with variable gradesof epithelial dysplasia (n = 13). The ductular epithelialcells were cuboidal with distinct cell borders and moderate amountsof eosinophilic cytoplasm. Often (n = 4), the nucleishowed karyomegaly and were hyperchromatic, containing one to threedistinct nucleoli (Figure 3B). Mitotic figureswere not present in the sections examined. In >50% of cases (n = 11), the ducts were ectatic and lined by hyperplasticepithelium that formed two or more layers (Figure 3A). Ductular adenomas (n = 3) were characterizedby the development of a 100–250 μm long papillary projectionfrom the ductular walls that narrowed the lumina (Figure 3A, inset). The neoplastic cells contained scantcytoplasm and round nuclei with one to three distinct nucleoli. Inall cases, desquamated epithelial cells were present within the ductularlumina. Prominent periductular fibrosis was a feature of all adenomas.Multifocal perivascular mast cell infiltration correlated with theseverity of the lesion in all cases. In addition, the ductular epithelialdysplasia correlated with the size of expansion of the terminal bud.


Chemopreventive and therapeutic activity of dietary blueberry against estrogen-mediated breast cancer.

Jeyabalan J, Aqil F, Munagala R, Annamalai L, Vadhanam MV, Gupta RC - J. Agric. Food Chem. (2014)

Presenceof epithelial dysplasia and ductular papillomas from mammarytissue of rats treated with E2 implant for 12 weeks. (A)Image of mammary section at 40× magnification showing long papillaryprojections from ductular walls (thin arrows) and ducts lined withhyperplastic epithelium with two or more layers (bold arrows). Insetshows 400× magnification of papillary projections. (B) Mammarysection at 600× magnification with nuclei showing karyomegaly,which are hyperchromatic containing one to three distinct nucleoli(thin arrows).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4334276&req=5

fig3: Presenceof epithelial dysplasia and ductular papillomas from mammarytissue of rats treated with E2 implant for 12 weeks. (A)Image of mammary section at 40× magnification showing long papillaryprojections from ductular walls (thin arrows) and ducts lined withhyperplastic epithelium with two or more layers (bold arrows). Insetshows 400× magnification of papillary projections. (B) Mammarysection at 600× magnification with nuclei showing karyomegaly,which are hyperchromatic containing one to three distinct nucleoli(thin arrows).
Mentions: In all animals that were treated withE2 for 12 weeks (n = 21), there was expansionof mammary tissue with proliferation of terminal buds that differentiatedinto acini. The acinar epithelial cells were frequently vacuolated,and the acini contained amphophilic inspissated secretory materialfilling the lumina (Figure 3A). Concomitantly,there was proliferation of ductules and ducts with variable gradesof epithelial dysplasia (n = 13). The ductular epithelialcells were cuboidal with distinct cell borders and moderate amountsof eosinophilic cytoplasm. Often (n = 4), the nucleishowed karyomegaly and were hyperchromatic, containing one to threedistinct nucleoli (Figure 3B). Mitotic figureswere not present in the sections examined. In >50% of cases (n = 11), the ducts were ectatic and lined by hyperplasticepithelium that formed two or more layers (Figure 3A). Ductular adenomas (n = 3) were characterizedby the development of a 100–250 μm long papillary projectionfrom the ductular walls that narrowed the lumina (Figure 3A, inset). The neoplastic cells contained scantcytoplasm and round nuclei with one to three distinct nucleoli. Inall cases, desquamated epithelial cells were present within the ductularlumina. Prominent periductular fibrosis was a feature of all adenomas.Multifocal perivascular mast cell infiltration correlated with theseverity of the lesion in all cases. In addition, the ductular epithelialdysplasia correlated with the size of expansion of the terminal bud.

Bottom Line: Berries are gaining increasing importance lately for their chemopreventive and therapeutic potential against several cancers.The effect on mammary tumorigenesis was largely due to down-regulation of CYP 1A1 and ER-α gene expression and also favorable modulation of microRNA (miR-18a and miR-34c) levels.These data suggest that the blueberry blend tested is effective in inhibiting E2-mediated mammary tumorigenesis in both preventive and therapeutic modes.

View Article: PubMed Central - PubMed

Affiliation: James Graham Brown Cancer Center, ‡Department of Medicine, and #Department of Pharmacology and Toxicology, University of Louisville , Louisville, Kentucky 40202, United States.

ABSTRACT
Berries are gaining increasing importance lately for their chemopreventive and therapeutic potential against several cancers. In earlier studies, a blueberry-supplemented diet has shown protection against 17β-estradiol (E2)-mediated mammary tumorigenesis. This study tested both preventive and therapeutic activities of diet supplemented with whole blueberry powder (50:50 blend of Tifblue and Rubel). Animals received 5% blueberry diet, either 2 weeks prior to or 12 weeks after E2 treatment in preventive and therapeutic groups, respectively. Both interventions delayed the tumor latency for palpable mammary tumors by 28 and 37 days, respectively. Tumor volume and multiplicity were also reduced significantly in both modes. The effect on mammary tumorigenesis was largely due to down-regulation of CYP 1A1 and ER-α gene expression and also favorable modulation of microRNA (miR-18a and miR-34c) levels. These data suggest that the blueberry blend tested is effective in inhibiting E2-mediated mammary tumorigenesis in both preventive and therapeutic modes.

Show MeSH
Related in: MedlinePlus