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Therapeutic potential of pharmacological targeting nlrp3 inflammasome complex in cancer

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dc.contributor.authorGaranina, Ekaterina E.
dc.contributor.authorAlsaadi, Mohammad
dc.contributor.authorGilazieva, Zarema E.
dc.contributor.authorMartinova, Ekaterina, V
dc.contributor.authorMarkelova, Maria, I
dc.contributor.authorArkhipova, Svetlana S.
dc.contributor.authorHamza, Shaimaa
dc.contributor.authorMcIntyre, Alan
dc.contributor.authorRizvanov, Albert A.
dc.contributor.authorKhaiboullina, Svetlana F.
dc.contributor.buuauthorTezcan, Gulcin
dc.contributor.buuauthorTEZCAN, GÜLÇİN
dc.contributor.departmentBursa Uludağ Üniversitesi/Diş Hekimliği Fakültesi.
dc.contributor.orcid0000-0002-5956-8755
dc.contributor.orcid0000-0001-7445-2091
dc.contributor.orcid0000-0002-4082-515X
dc.contributor.orcid0000-0002-5012-4760
dc.contributor.orcid0000-0002-4791-7292
dc.contributor.orcid0000-0002-9427-5739
dc.contributor.researcheridAAH-3843-2020
dc.contributor.researcheridH-4486-2013
dc.contributor.researcheridHTO-8900-2023
dc.contributor.researcheridAAE-4652-2022
dc.contributor.researcheridAAP-5140-2021
dc.contributor.researcheridW-9788-2018
dc.contributor.researcheridP-4183-2017
dc.date.accessioned2024-06-25T13:21:02Z
dc.date.available2024-06-25T13:21:02Z
dc.date.issued2021-02-03
dc.description.abstractIntroductionDysregulation of NLRP3 inflammasome complex formation can promote chronic inflammation by increased release of IL-1 beta. 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 in-vitro.MethodThe 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-1 beta 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.ResultsLPS/Nigericin increased NRLP3 protein expression as well as IL-1 beta 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.DiscussionOur 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-1 beta and IL-18.
dc.description.sponsorshipUK Research & Innovation (UKRI) Medical Research Council UK (MRC) -- MR/P010334/1
dc.identifier.doi10.3389/fimmu.2020.607881
dc.identifier.issn1664-3224
dc.identifier.urihttps://doi.org/10.3389/fimmu.2020.607881
dc.identifier.urihttps://hdl.handle.net/11452/42383
dc.identifier.volume11
dc.identifier.wos000618657800001
dc.indexed.wosWOS.SCI
dc.language.isoen
dc.publisherFrontiers Media Sa
dc.relation.journalFrontiers In Immunology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectNlrp3
dc.subjectInflammasome
dc.subjectCancer
dc.subjectIl-1&#946
dc.subjectNigericin
dc.subjectScience & technology
dc.subjectLife sciences & biomedicine
dc.subjectImmunology
dc.subjectImmunology
dc.titleTherapeutic potential of pharmacological targeting nlrp3 inflammasome complex in cancer
dc.typeArticle
dspace.entity.typePublication
relation.isAuthorOfPublicatione171a866-0a2e-4df4-9f4b-d9058971c979
relation.isAuthorOfPublication.latestForDiscoverye171a866-0a2e-4df4-9f4b-d9058971c979

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