Therapeutic Potential of Pharmacological Targeting NLRP3 Inflammasome Complex in Cancer.
A549 Cells
Antineoplastic Agents
/ pharmacology
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Cytokines
/ metabolism
Dipeptides
/ pharmacology
Humans
Inflammasomes
/ agonists
Inflammation Mediators
/ metabolism
MCF-7 Cells
Mitochondria
/ drug effects
Molecular Targeted Therapy
NLR Family, Pyrin Domain-Containing 3 Protein
/ agonists
Neoplasms
/ drug therapy
Neovascularization, Pathologic
Nigericin
/ pharmacology
PC-3 Cells
Signal Transduction
para-Aminobenzoates
/ pharmacology
IL-1β
NLRP3
cancer
inflammasome
nigericin
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
18
09
2020
accepted:
17
12
2020
entrez:
22
2
2021
pubmed:
23
2
2021
medline:
24
6
2021
Statut:
epublish
Résumé
Dysregulation of NLRP3 inflammasome complex formation can promote chronic inflammation by increased release of IL-1β. However, the effect of NLRP3 complex formation on tumor progression remains controversial. Therefore, we sought to determine the effect of NLRP3 modulation on the growth of the different types of cancer cells, derived from lung, breast, and prostate cancers as well as neuroblastoma and glioblastoma The effect of Caspase 1 inhibitor (VX765) and combination of LPS/Nigericin on NLRP3 inflammasome activity was analyzed in A549 (lung cancer), MCF-7 (breast cancer), PC3 (prostate cancer), SH-SY5Y (neuroblastoma), and U138MG (glioblastoma) cells. Human fibroblasts were used as control cells. The effect of VX765 and LPS/Nigericin on NLRP3 expression was analyzed using western blot, while IL-1β and IL-18 secretion was detected by ELISA. Tumor cell viability and progression were determined using Annexin V, cell proliferation assay, LDH assay, sphere formation assay, transmission electron microscopy, and a multiplex cytokine assay. Also, angiogenesis was investigated by a tube formation assay. VEGF and MMPs secretion were detected by ELISA and a multiplex assay, respectively. Statistical analysis was done using one-way ANOVA with Tukey's analyses and Kruskal-Wallis one-way analysis of variance. LPS/Nigericin increased NRLP3 protein expression as well as IL-1β and IL-18 secretion in PC3 and U138MG cells compared to A549, MCF7, SH-SY5Y cells, and fibroblasts. In contrast, MIF expression was commonly found upregulated in A549, PC3, SH-SY5Y, and U138MG cells and fibroblasts after Nigericin treatment. Nigericin and a combination of LPS/Nigericin decreased the cell viability and proliferation. Also, LPS/Nigericin significantly increased tumorsphere size in PC3 and U138MG cells. In contrast, the sphere size was reduced in MCF7 and SH-SY5Y cells treated with LPS/Nigericin, while no effect was detected in A549 cells. VX765 increased secretion of CCL24 in A549, MCF7, PC3, and fibroblasts as well as CCL11 and CCL26 in SH-SY5Y cells. Also, VX765 significantly increased the production of VEGF and MMPs and stimulated angiogenesis in all tumor cell lines. Our data suggest that NLRP3 activation using Nigericin could be a novel therapeutic approach to control the growth of tumors producing a low level of IL-1β and IL-18.
Identifiants
pubmed: 33613529
doi: 10.3389/fimmu.2020.607881
pmc: PMC7887322
doi:
Substances chimiques
Antineoplastic Agents
0
Cytokines
0
Dipeptides
0
Inflammasomes
0
Inflammation Mediators
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
NLRP3 protein, human
0
para-Aminobenzoates
0
belnacasan
00OLE78529
Nigericin
RRU6GY95IS
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
607881Subventions
Organisme : Medical Research Council
ID : MR/P010334/1
Pays : United Kingdom
Informations de copyright
Copyright © 2021 Tezcan, Garanina, Alsaadi, Gilazieva, Martinova, Markelova, Arkhipova, Hamza, McIntyre, Rizvanov and Khaiboullina.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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