Organic Selenium induces ferroptosis in pancreatic cancer cells.
Dibenzyl diselenide (DBDS)
Ferroptosis
Mevalonate pathway (MVP)
Pancreatic cancer
Selenorganic compounds
Journal
Redox biology
ISSN: 2213-2317
Titre abrégé: Redox Biol
Pays: Netherlands
ID NLM: 101605639
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
17
10
2023
accepted:
10
11
2023
medline:
6
12
2023
pubmed:
29
11
2023
entrez:
29
11
2023
Statut:
ppublish
Résumé
Pancreatic ductal adenocarcinoma (PDA) cells reprogram both mitochondrial and lysosomal functions to support growth. At the same time, this causes significant dishomeostasis of free radicals. While this is compensated by the upregulation of detoxification mechanisms, it also represents a potential vulnerability. Here we demonstrate that PDA cells are sensitive to the inhibition of the mevalonate pathway (MVP), which supports the biosynthesis of critical antioxidant intermediates and protect from ferroptosis. We attacked the susceptibility of PDA cells to ferroptotic death with selenorganic compounds, including dibenzyl diselenide (DBDS) that exhibits potent pro-oxidant properties and inhibits tumor growth in vitro and in vivo. DBDS treatment induces the mobilization of iron from mitochondria enabling uncontrolled lipid peroxidation. Finally, we showed that DBDS and statins act synergistically to promote ferroptosis and provide evidence that combined treatment is a viable strategy to combat PDA.
Identifiants
pubmed: 38029455
pii: S2213-2317(23)00363-4
doi: 10.1016/j.redox.2023.102962
pmc: PMC10698006
pii:
doi:
Substances chimiques
Selenium
H6241UJ22B
4,4'-dibenzamido-2,2'-stilbenedisulfonic acid
7342-14-5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102962Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest None.
Références
Cell. 2018 Jan 25;172(3):409-422.e21
pubmed: 29290465
Cancer Res. 2022 Oct 04;82(19):3486-3498
pubmed: 35916672
Cell Metab. 2020 Dec 1;32(6):920-937
pubmed: 33217331
Biochim Biophys Acta. 2015 Aug;1850(8):1642-60
pubmed: 25459512
Redox Biol. 2021 Sep;45:102021
pubmed: 34102574
Biochim Biophys Acta. 2006 Sep-Oct;1757(9-10):1338-56
pubmed: 16987493
Elife. 2022 Jul 29;11:
pubmed: 35904245
Redox Biol. 2022 May;51:102272
pubmed: 35255427
Cell Rep. 2019 Aug 13;28(7):1845-1859.e5
pubmed: 31412251
Redox Biol. 2022 Apr;50:102232
pubmed: 35101798
Redox Biol. 2016 Aug;8:439-41
pubmed: 26848025
J Mater Chem B. 2023 Jan 4;11(2):325-334
pubmed: 36484416
Redox Biol. 2020 Jan;28:101328
pubmed: 31574461
Cancer Discov. 2022 Sep 2;12(9):2180-2197
pubmed: 35771492
Trends Cancer. 2021 Oct;7(10):891-901
pubmed: 34023326
Nat Rev Cancer. 2016 Nov;16(11):718-731
pubmed: 27562463
J Biol Chem. 2022 Mar;298(3):101617
pubmed: 35065965
Cell Rep. 2021 Nov 23;37(8):110056
pubmed: 34818551
Nat Commun. 2020 Dec 11;11(1):6339
pubmed: 33311482
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Cell Metab. 2016 Nov 8;24(5):716-727
pubmed: 27746050
Free Radic Biol Med. 2018 Nov 1;127:80-97
pubmed: 29746900
Nat Rev Gastroenterol Hepatol. 2021 Nov;18(11):804-823
pubmed: 34331036
PLoS One. 2020 Jan 30;15(1):e0228015
pubmed: 31999765
Nat Chem Biol. 2022 Jul;18(7):751-761
pubmed: 35637349
Oncogene. 2012 Nov 29;31(48):4967-78
pubmed: 22310279
Cancer Discov. 2019 Mar;9(3):416-435
pubmed: 30626590
Cancer Res. 2020 Jan 15;80(2):175-188
pubmed: 31562248
J Am Chem Soc. 2012 Apr 11;134(14):6479-90
pubmed: 22424175
Nature. 2016 Apr 14;532(7598):245-9
pubmed: 27049944
Cancer Res. 2020 Jan 15;80(2):189-203
pubmed: 31744820
Redox Biol. 2021 May;41:101877
pubmed: 33607499
Nat Rev Mol Cell Biol. 2021 Apr;22(4):266-282
pubmed: 33495651
Immunol Rev. 2017 May;277(1):150-157
pubmed: 28462529
Mol Cell. 2023 Apr 6;83(7):1030-1042
pubmed: 36977413
Immunity. 2018 Jul 17;49(1):178-193.e7
pubmed: 29958801
Mol Cell. 2022 Aug 18;82(16):3045-3060.e11
pubmed: 35752173
Cancer Discov. 2022 Sep 2;12(9):2198-2219
pubmed: 35771494
Nat Cell Biol. 2014 Dec;16(12):1180-91
pubmed: 25402683
Molecules. 2019 Aug 11;24(16):
pubmed: 31405214
J Biol Chem. 2009 Jan 9;284(2):723-7
pubmed: 18757362
Proc Natl Acad Sci U S A. 2010 May 11;107(19):8788-93
pubmed: 20421486
Cell. 2016 Aug 11;166(4):963-976
pubmed: 27477511
Annu Rev Physiol. 2019 Feb 10;81:453-482
pubmed: 30485761
Nat Rev Cancer. 2022 May;22(5):280-297
pubmed: 35102280
Cell. 2017 Oct 19;171(3):696-709.e23
pubmed: 28965760
Free Radic Biol Med. 2015 Nov;88(Pt B):466-480
pubmed: 26151571
J Nanobiotechnology. 2021 Oct 9;19(1):311
pubmed: 34627266
EMBO J. 2021 Mar 1;40(5):e106700
pubmed: 33439509
Nat Cell Biol. 2014 Aug;16(8):728-36
pubmed: 25082195
Cell Chem Biol. 2020 Apr 16;27(4):409-419
pubmed: 32275866
Curr Opin Physiol. 2022 Feb;25:
pubmed: 35342847
Elife. 2022 Jul 11;11:
pubmed: 35815941
Antioxid Redox Signal. 2016 May 10;24(14):781-94
pubmed: 26714745
Antioxid Redox Signal. 2018 Jul 1;29(1):61-74
pubmed: 28462584
Cell. 2017 Oct 5;171(2):273-285
pubmed: 28985560
iScience. 2022 Feb 24;25(3):103980
pubmed: 35310338
Nature. 2017 Jul 27;547(7664):453-457
pubmed: 28678785
Nature. 2019 Nov;575(7784):688-692
pubmed: 31634900
Molecules. 2021 Jul 12;26(14):
pubmed: 34299505
Nat Cell Biol. 2022 Feb;24(2):168-180
pubmed: 35165418
Mitochondrion. 2015 Mar;21:92-105
pubmed: 25667951
Science. 2020 Apr 3;368(6486):85-89
pubmed: 32241947
Nat Chem Biol. 2016 Jul;12(7):497-503
pubmed: 27159577
Mol Cell. 2019 Jan 17;73(2):354-363.e3
pubmed: 30581146
Nature. 2021 May;593(7860):586-590
pubmed: 33981038
Redox Biol. 2021 Jan;38:101807
pubmed: 33271455
Cell Death Differ. 2018 Mar;25(3):486-541
pubmed: 29362479
Cell Death Differ. 2017 Dec;24(12):1991-1998
pubmed: 28984871
Blood. 2012 May 3;119(18):4253-63
pubmed: 22411871
Int J Mol Sci. 2023 Aug 10;24(16):
pubmed: 37628814
Nat Cell Biol. 2023 Feb;25(2):246-257
pubmed: 36658222
Proc Natl Acad Sci U S A. 2013 May 28;110(22):8882-7
pubmed: 23671091
Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):10775-82
pubmed: 20495089