NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma Progression.
Animals
Carcinoma, Squamous Cell
/ drug therapy
Cell Proliferation
/ drug effects
Disease Progression
Humans
Inflammasomes
/ antagonists & inhibitors
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Mouth Neoplasms
/ drug therapy
NLR Family, Pyrin Domain-Containing 3 Protein
/ antagonists & inhibitors
Nitriles
/ pharmacology
Sulfones
/ pharmacology
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
NOD-like receptor family pyrin domain containing 3 inflammasome (NLRP3)
apoptosis
oral cancer
oral squamous cell carcinoma (OSCC)
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
15 Oct 2021
15 Oct 2021
Historique:
received:
16
09
2021
revised:
07
10
2021
accepted:
11
10
2021
entrez:
23
10
2021
pubmed:
24
10
2021
medline:
20
1
2022
Statut:
epublish
Résumé
Oral cancer is one of the most common human malignancies, and its incidence is increasing worldwide. In particular, oral squamous cell carcinoma (OSCC) is characterized by high rates of proliferation, invasiveness, and metastasis. Currently, standard treatment for OSCC includes surgical removal, chemotherapy, and radiotherapy; however, the survival rate of patients with OSCC remains low, thus new therapies are needed. It has been proven that excessive NLRP3 inflammasome activation and apoptosis alteration may contribute to oral cancer progression. This study aimed to investigate the effect of BAY-117082, an NLRP3 inflammasome inhibitor, in an in vitro and in vivo xenograft model of oral cancer. In vitro results revealed that BAY-117082 at concentrations of 5, 10, and 30 µM was able to reduce OSCC cell viability. BAY-117082 at higher concentrations significantly reduced NLRP3, ASC, caspase-1, IL-1β, and IL-18 expression. Moreover, Bax, Bad, and p53 expression were increased, whereas Bcl-2 expression was reduced. Furthermore, the in vivo study demonstrated that BAY-117082 at doses of 2.5 and 5 mg/kg significantly decreased subcutaneous tumor mass, and also reduced NLRP3 inflammasome pathway activation. Therefore, based on these results, the use of BAY-117082 could be considered a promising strategy to counteract oral cancer progression, thanks its ability to modulate the NLRP3 inflammasome and apoptosis pathways.
Identifiants
pubmed: 34681768
pii: ijms222011108
doi: 10.3390/ijms222011108
pmc: PMC8540383
pii:
doi:
Substances chimiques
3-(4-methylphenylsulfonyl)-2-propenenitrile
0
Inflammasomes
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
Nitriles
0
Sulfones
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Références
Cold Spring Harb Perspect Biol. 2013 Feb 01;5(2):
pubmed: 23378584
Neoplasia. 2018 Apr;20(4):374-386
pubmed: 29529473
Asian Pac J Cancer Prev. 2015;16(6):2129-44
pubmed: 25824729
Cancers (Basel). 2021 May 11;13(10):
pubmed: 34064909
Mol Cancer Ther. 2009 Sep;8(9):2635-44
pubmed: 19723887
Oral Oncol. 2009 Nov;45(11):e204-7
pubmed: 19631575
Oncoimmunology. 2015 Oct 20;5(1):e1005522
pubmed: 26942050
Cell Physiol Biochem. 2013;32(4):801-13
pubmed: 24080940
Trends Pharmacol Sci. 2003 Mar;24(3):139-45
pubmed: 12628359
J Dent Res. 2012 May;91(5):447-53
pubmed: 21972258
Med Sci Monit Basic Res. 2017 Apr 07;23:141-149
pubmed: 28386055
J Exp Clin Cancer Res. 2017 Sep 2;36(1):116
pubmed: 28865486
Mol Neurobiol. 2020 Nov;57(11):4394-4407
pubmed: 32729104
Chromosoma. 2018 Jun;127(2):175-186
pubmed: 29322240
Adv Pharm Bull. 2019 Jun;9(2):205-218
pubmed: 31380246
BMC Cancer. 2018 May 2;18(1):500
pubmed: 29716544
Theranostics. 2019 May 18;9(11):3293-3307
pubmed: 31244955
Exp Suppl. 2018;108:153-176
pubmed: 30536171
J Cell Biochem. 2008 Jul 1;104(4):1124-49
pubmed: 18459149
Oxid Med Cell Longev. 2020 Feb 17;2020:4063562
pubmed: 32148650
Front Oncol. 2018 Oct 15;8:442
pubmed: 30460193
Front Immunol. 2019 Jun 07;10:1197
pubmed: 31231372
Toxicol Pathol. 2007 Jun;35(4):495-516
pubmed: 17562483
Biosci Rep. 2018 Nov 20;38(6):
pubmed: 30341240
Cancers (Basel). 2021 Jul 09;13(14):
pubmed: 34298658
PLoS One. 2013;8(3):e59292
pubmed: 23527154
Biomedicines. 2020 Nov 20;8(11):
pubmed: 33233503
J Cell Physiol. 2015 Apr;230(4):875-84
pubmed: 25204733
Surg Oncol Clin N Am. 2015 Jul;24(3):491-508
pubmed: 25979396
Br J Cancer. 2019 Apr;120(7):714-727
pubmed: 30808992
J Clin Invest. 2015 Sep;125(9):3347-55
pubmed: 26325032
Oncogene. 2006 Aug 7;25(34):4798-811
pubmed: 16892092
Curr Protoc Cell Biol. 2015 Dec 01;69:4.3.1-4.3.7
pubmed: 26621373
Immunol Rev. 2011 Sep;243(1):174-90
pubmed: 21884176
Front Immunol. 2018 Oct 16;9:2379
pubmed: 30459758
BMC Cancer. 2010 Aug 17;10:437
pubmed: 20716363
Lancet Oncol. 2010 Aug;11(8):781-9
pubmed: 20451455
Crit Rev Oral Biol Med. 2002;13(1):51-61
pubmed: 12097237
Eur Rev Med Pharmacol Sci. 2018 May;22(9):2564-2571
pubmed: 29771406
J Biol Chem. 2010 Mar 26;285(13):9792-9802
pubmed: 20093358
Front Pharmacol. 2017 May 22;8:278
pubmed: 28588486
Biomedicines. 2021 Jul 02;9(7):
pubmed: 34356835
Periodontol 2000. 2011 Oct;57(1):19-37
pubmed: 21781177
Crit Rev Oncol Hematol. 2014 Jun;90(3):200-19
pubmed: 24507955
Mol Cancer. 2018 Nov 17;17(1):158
pubmed: 30447690
Tumour Biol. 2017 May;39(5):1010428317705330
pubmed: 28513299
J Gastroenterol. 2014 May;49(5):864-74
pubmed: 23846545
Mol Med Rep. 2015 Mar;11(3):1566-72
pubmed: 25384676
Nat Rev Cancer. 2014 May;14(5):359-70
pubmed: 24739573