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.

Chronic treatment with resveratrol and olive oil phenols on MRC5 fibroblast SASP: inhibition of pro-tumoral microenvironment / Beatrice Menicacci, Anna Laurenzana, Anastasia Chillà, Francesca Margheri, Gabriella Fibbi, lisa Giovannelli, Mario Del Rosso and Alessandra Mocali. - ELETTRONICO. - (2017), pp. 0-0. (Intervento presentato al convegno International Cell Senescence Association (ICSA) Conference 2017 tenutosi a Parigi nel 16-19 maggio 2017).

Chronic treatment with resveratrol and olive oil phenols on MRC5 fibroblast SASP: inhibition of pro-tumoral microenvironment

Beatrice Menicacci;Anna Laurenzana;Anastasia Chillà;Francesca Margheri;Gabriella Fibbi;lisa Giovannelli;
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.
2017
International Cell Senescence Association (ICSA) Conference 2017
International Cell Senescence Association (ICSA) Conference 2017
Parigi
Beatrice Menicacci, Anna Laurenzana, Anastasia Chillà, Francesca Margheri, Gabriella Fibbi, lisa Giovannelli, Mario Del Rosso and Alessandra Mocali
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1120077
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