NDLI: Hydroxytyrosol inhibits chemokine C-C motif ligand 5 mediated aged quiescent fibroblast-induced stimulation of breast cancer cell proliferation

Content Provider	PubMed Central
Author	Sarsour, Ehab H. Goswami, Monali Kalen, Amanda L. Lafin, John T. Goswami, Prabhat C.
Abstract	Cancer is an age-associated disease. Although the mechanisms of age-associated increase in cancer incidence are not completely understood, it is believed that the tumor stromal environment significantly influences epithelial malignancy. Fibroblasts are a major cell type in the stroma and, under normal conditions, fibroblasts reside in the quiescent state. Cellular quiescence is a reversible process where cells enter into the proliferative cycle and then exit back to quiescence. We have shown previously that quiescent fibroblasts lose their proliferative capacity as they age, and we defined this mode of cellular aging as chronological life span. Using conditioned media and co-culture experiments, results from this study show that normal human fibroblasts (NHFs) nearing the end of their chronological life span stimulate the proliferation of MB231 and MCF7 human breast epithelial cancer cells. Chemokine C-C motif ligand 5 (CCL5) expression was found to be approximately 8-fold higher in old compared to that in young quiescent NHFs, which correlated with an increase in the ERK1/2-cyclin D1 pro-proliferative pathway in MB231 cells. Conditioned media treated with anti-CCL5 antibody suppressed the activation of the ERK1/2-cyclin D1 pathway and proliferation of MB231 cells. Hydroxytyrosol, a dietary polyphenol and an active ingredient of olive, inhibited CCL5 expression in aging quiescent NHFs. This inhibition was associated with NHFs inability to activate the ERK1/2-cyclin D1 pathway and enhance proliferation of MB231 cells. These results show that fibroblasts nearing the end of their chronological life span promote proliferation of human breast epithelial cancer cells and dietary polyphenols inhibit this process.
Related Links	http://dx.doi.org/10.1007/s11357-014-9645-0
Starting Page	9645
File Format	PDF
ISSN	01619152
e-ISSN	15744647
Journal	Age
Issue Number	3
Volume Number	36
Language	English
Publisher	Springer Netherlands
Publisher Date	2014-06-01
Access Restriction	Open
Rights Holder	Springer Netherlands
Subject Keyword	Ageing Geriatrics and Gerontology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Aging Geriatrics and Gerontology

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