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Chronic Resveratrol Treatment Inhibits MRC5 Fibroblast SASP-Related Protumoral Effects on Melanoma Cells.
- Source :
-
The journals of gerontology. Series A, Biological sciences and medical sciences [J Gerontol A Biol Sci Med Sci] 2017 Sep 01; Vol. 72 (9), pp. 1187-1195. - Publication Year :
- 2017
-
Abstract
- Cellular senescence is related to organismal aging and is observed after DNA damaging cancer therapies, that induce tumor-suppressive modifications, but it is characterized by a strong increase in secreted factors, termed the "senescence-associated secretory phenotype" (SASP). Particularly, SASP from stroma senescent fibroblasts creates a cancer-favoring microenvironment, providing targets for anti-cancer interventions. In the present article, chronic treatment (5 weeks) with 5 µM resveratrol has been used to modulate senescence-related protumoral features of MRC5 fibroblasts, reducing SASP-related interleukins IL1α, IL1β, IL6, and IL8; transforming-growth-factor-β (TGFβ); matrix metallo-proteinases MMP3 and MMP2; urokinase plasminogen activator (uPA); receptor proteins uPAR, IL6R, insulin growth factor receptor-1 (IGF-1R), TGFβ-R2, and CXCR4. The cellular nuclear-factor-kB (NF-kB) protein level was also reduced, confirming its role in the induction of SASP. Resveratrol pretreated MRC5 fibroblasts were resistant to activation by TGFβ. Resveratrol treatment of senescent MRC5 induced the production of conditioned media (CM) which counteracted the protumoral effect of senescent CM on A375 and A375-M6 melanoma cell proliferation and invasiveness, and reduced the expression of epithelial-to-mesenchymal transition markers related to malignant features. This experimental approach proposes a treatment that targets the senescent stromal cell phenotype to induce an anti-tumor hosting microenvironment, which is suitable for both preventive and therapeutic purposes.<br /> (© The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Animals
Biomarkers, Tumor metabolism
Blotting, Western
Cell Line, Tumor
Cell Proliferation drug effects
Culture Media, Conditioned
Humans
Interleukins metabolism
Mice
Phenotype
Real-Time Polymerase Chain Reaction
Resveratrol
Tumor Microenvironment
Cellular Senescence drug effects
Fibroblasts drug effects
Melanoma drug therapy
Stilbenes pharmacology
Tumor Cells, Cultured drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1758-535X
- Volume :
- 72
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The journals of gerontology. Series A, Biological sciences and medical sciences
- Publication Type :
- Academic Journal
- Accession number :
- 28329136
- Full Text :
- https://doi.org/10.1093/gerona/glw336