Olive phenols preserve lamin B1 expression reducing cGAS/STING/NFκB-mediated SASP in ionizing radiation-induced senescence.
DNA damage
SASP
human fibroblasts
polyphenols
radiation-induced senescence
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
revised:
04
02
2022
received:
21
06
2021
accepted:
11
02
2022
pubmed:
13
3
2022
medline:
13
4
2022
entrez:
12
3
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35278036
doi: 10.1111/jcmm.17255
pmc: PMC8995441
doi:
Substances chimiques
Lamin Type B
0
NF-kappa B
0
Phenols
0
Nucleotidyltransferases
EC 2.7.7.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2337-2350Subventions
Organisme : Fondazione Umberto Veronesi (Dr. Manuela Leri)
Organisme : ANCC-COOP/Airalzh ONLUS (Dr. Manuela Leri)
ID : 0043966.30-10-359 2014-u
Organisme : Global Marie Curie Fellowship (Dr. Anastasia Chillà)
Organisme : Ente Cassa di Risparmio di Firenze
ID : 2020.201683
Informations de copyright
© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
Références
Nat Rev Cancer. 2019 Aug;19(8):439-453
pubmed: 31235879
J Neurosci Res. 2000 Jun 1;60(5):613-22
pubmed: 10820432
J Gerontol A Biol Sci Med Sci. 2011 Jan;66(1):9-18
pubmed: 20884849
J Cell Mol Med. 2009 Jun;13(6):1059-85
pubmed: 19210577
Nat Cell Biol. 2017 Sep;19(9):1061-1070
pubmed: 28759028
Trends Mol Med. 2010 May;16(5):238-46
pubmed: 20444648
PLoS One. 2014 May 08;9(5):e96351
pubmed: 24810370
Int J Mol Sci. 2020 Apr 08;21(7):
pubmed: 32276415
Immun Ageing. 2015 Nov 04;12:20
pubmed: 26543490
Genes Dev. 1994 Nov 1;8(21):2540-51
pubmed: 7958916
Eur J Immunol. 1999 Feb;29(2):700-12
pubmed: 10064088
J Cell Mol Med. 2022 Apr;26(8):2337-2350
pubmed: 35278036
Clin Nutr. 2011 Aug;30(4):533-40
pubmed: 21411195
Int J Mol Sci. 2021 Jan 27;22(3):
pubmed: 33513799
Antioxidants (Basel). 2020 Sep 03;9(9):
pubmed: 32899274
Rejuvenation Res. 2007 Jun;10(2):157-72
pubmed: 17518699
PLoS Biol. 2008 Dec 2;6(12):2853-68
pubmed: 19053174
Nat Rev Mol Cell Biol. 2007 Sep;8(9):729-40
pubmed: 17667954
Methods Mol Biol. 2013;965:63-81
pubmed: 23296651
J Gerontol A Biol Sci Med Sci. 2017 Sep 1;72(9):1187-1195
pubmed: 28329136
Curr Mol Med. 2017;17(2):149-159
pubmed: 28429673
Nutr Cancer. 2019;71(2):320-333
pubmed: 30661406
Circulation. 2014 Sep 9;130(11):880-891
pubmed: 24993099
Antioxidants (Basel). 2019 Nov 22;8(12):
pubmed: 31766676
Int J Biochem Cell Biol. 2005 May;37(5):961-76
pubmed: 15743671
J Vet Med Sci. 2018 Dec 11;80(12):1801-1807
pubmed: 30298817
Mutat Res Genet Toxicol Environ Mutagen. 2019 Jul;843:11-17
pubmed: 31421731
Exp Mol Med. 2018 May 14;50(5):1-12
pubmed: 29760459
J Gerontol A Biol Sci Med Sci. 2019 Apr 23;74(5):625-633
pubmed: 30084946
Nat Rev Genet. 2019 Nov;20(11):657-674
pubmed: 31358977
Aging Cell. 2018 Apr;17(2):
pubmed: 29290100
Science. 2019 Mar 8;363(6431):
pubmed: 30846571
Free Radic Biol Med. 2018 Feb 1;115:80-91
pubmed: 29080843
J Natl Cancer Inst. 2010 Oct 20;102(20):1536-46
pubmed: 20858887
Expert Opin Ther Targets. 2013 Dec;17(12):1439-60
pubmed: 24090198
Genes Dev. 2013 Aug 15;27(16):1800-8
pubmed: 23964094
Cancer Manag Res. 2020 Dec 31;12:13553-13566
pubmed: 33408525
Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9363-7
pubmed: 7568133
Mol Biol Cell. 2012 Jun;23(11):2066-75
pubmed: 22496421
Nat Rev Neurosci. 2007 Oct;8(10):766-75
pubmed: 17882254
Annu Rev Physiol. 2013;75:685-705
pubmed: 23140366
Biochem J. 1998 May 15;332 ( Pt 1):43-50
pubmed: 9576849
Int J Mol Sci. 2017 Oct 30;18(11):
pubmed: 29084133
Aging Cell. 2015 Feb;14(1):1-7
pubmed: 25399755
Nature. 2006 Nov 30;444(7119):633-7
pubmed: 17136093
Curr Cancer Drug Targets. 2013 Jul;13(6):625-39
pubmed: 23597197
Am J Physiol Gastrointest Liver Physiol. 2014 Aug 1;307(3):G330-7
pubmed: 24875103
Sci Pharm. 2010;78(2):133-54
pubmed: 21179340
Exp Cell Res. 1961 Dec;25:585-621
pubmed: 13905658
Antioxid Redox Signal. 2010 Dec 1;13(11):1763-811
pubmed: 20446769
J Nutr Biochem. 2010 Aug;21(8):726-35
pubmed: 19616928
Nature. 2017 Oct 19;550(7676):402-406
pubmed: 28976970
Nat Cell Biol. 2013 Aug;15(8):978-90
pubmed: 23770676
Genes Dev. 2020 Mar 1;34(5-6):428-445
pubmed: 32001510
Nature. 1990 May 31;345(6274):458-60
pubmed: 2342578