Senescence occurs upon critical telomere shortening, or following DNA damage, oncogenic activation, hypoxia and oxidative stress, overall referred to stress-induced premature senescence (SIPS). In response to DNA damage, senescent cells release cytoplasmic chromatin fragments (CCFs), and express an altered secretome, the senescence-associated secretory phenotype (SASP), which contributes to generate a pro-inflammatory and pro-tumoral extracellular milieu. Polyphenols have gained significant attention owing to their anti-inflammatory and anti-tumour activities. Here, we studied the effect of oleuropein aglycone (OLE) and hydroxytyrosol (HT) on DNA damage, CCF appearance and SASP in a model of irradiation-induced senescence. Neonatal human dermal fibroblasts (NHDFs) were γ-irradiated and incubated with OLE, 5 µM and HT, 1 µM. Cell growth and senescence-associated (SA)-β-Gal-staining were used as senescence markers. DNA damage was evaluated by Comet assay, lamin B1 expression, release of CCFs, cyclic GMP-AMP Synthase (cGAS) activation. IL-6, IL-8, MCP-1 and RANTES were measured by ELISA assay. Our results showed that OLE and HT exerted a protective effect on 8 Gy irradiation-induced senescence, preserving lamin B1 expression and reducing cGAS/STING/NFκB-mediated SASP. The ability of OLE and HT to mitigate DNA damage, senescence status and the related SASP in normal cells can be exploited to improve the efficacy and safety of cancer radiotherapy.

Olive phenols preserve lamin B1 expression reducing cGAS/STING/NFκB-mediated SASP in ionizing radiation-induced senescence / Elena Frediani, Francesca Scavone, Anna Laurenzana, Anastasia Chillà, Katia Tortora, Ilaria Cimmino, Manuela Leri, Monica Bucciantini, Monica Mangoni, Gabriella Fibbi, Mario Del Rosso, Alessandra Mocali, Lisa Giovannelli, Francesca Margheri. - In: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE. - ISSN 1582-4934. - ELETTRONICO. - 26:(2022), pp. 2337-2350. [10.1111/jcmm.17255]

Olive phenols preserve lamin B1 expression reducing cGAS/STING/NFκB-mediated SASP in ionizing radiation-induced senescence.

Elena Frediani;Francesca Scavone;Anna Laurenzana;Anastasia Chillà;Katia Tortora;Manuela Leri;Monica Bucciantini;Monica Mangoni;Gabriella Fibbi;Mario Del Rosso;Alessandra Mocali;Lisa Giovannelli;Francesca Margheri
2022

Abstract

Senescence occurs upon critical telomere shortening, or following DNA damage, oncogenic activation, hypoxia and oxidative stress, overall referred to stress-induced premature senescence (SIPS). In response to DNA damage, senescent cells release cytoplasmic chromatin fragments (CCFs), and express an altered secretome, the senescence-associated secretory phenotype (SASP), which contributes to generate a pro-inflammatory and pro-tumoral extracellular milieu. Polyphenols have gained significant attention owing to their anti-inflammatory and anti-tumour activities. Here, we studied the effect of oleuropein aglycone (OLE) and hydroxytyrosol (HT) on DNA damage, CCF appearance and SASP in a model of irradiation-induced senescence. Neonatal human dermal fibroblasts (NHDFs) were γ-irradiated and incubated with OLE, 5 µM and HT, 1 µM. Cell growth and senescence-associated (SA)-β-Gal-staining were used as senescence markers. DNA damage was evaluated by Comet assay, lamin B1 expression, release of CCFs, cyclic GMP-AMP Synthase (cGAS) activation. IL-6, IL-8, MCP-1 and RANTES were measured by ELISA assay. Our results showed that OLE and HT exerted a protective effect on 8 Gy irradiation-induced senescence, preserving lamin B1 expression and reducing cGAS/STING/NFκB-mediated SASP. The ability of OLE and HT to mitigate DNA damage, senescence status and the related SASP in normal cells can be exploited to improve the efficacy and safety of cancer radiotherapy.
2022
26
2337
2350
Elena Frediani, Francesca Scavone, Anna Laurenzana, Anastasia Chillà, Katia Tortora, Ilaria Cimmino, Manuela Leri, Monica Bucciantini, Monica Mangoni, Gabriella Fibbi, Mario Del Rosso, Alessandra Mocali, Lisa Giovannelli, Francesca Margheri
File in questo prodotto:
File Dimensione Formato  
J Cellular Molecular Medi - 2022 - Frediani - Olive phenols preserve lamin B1 expression reducing cGAS STING NF B‐mediated.pdf

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: Creative commons
Dimensione 1.75 MB
Formato Adobe PDF
1.75 MB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1260646
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 9
  • ???jsp.display-item.citation.isi??? 8
social impact