Please use this identifier to cite or link to this item: https://ninho.inca.gov.br/jspui/handle/123456789/12052
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dc.contributor.authorWerneck, Miriam Bianchi de Frontin-
dc.contributor.authorHottz, Eugenio Damaceno-
dc.contributor.authorViola, Patricia Torres Bozza-
dc.contributor.authorViola, Joao Paulo de Biaso-
dc.date.accessioned2022-12-26T12:02:52Z-
dc.date.available2022-12-26T12:02:52Z-
dc.date.issued2012-11-
dc.identifier.issn1551-4005-
dc.identifier.urihttps://ninho.inca.gov.br/jspui/handle/123456789/12052-
dc.description.abstractChronic inflammation is a risk factor for the development of colon cancer, providing genotoxic insults, growth and pro angiogenic factors that can promote tumorigenesis and tumor growth. Immunomodulatory agents can interfere with the inflammation that feeds cancer, but their impact on the transformed cell is poorly understood. The calcium/calcineurin signaling pathway, through activation of NFAT, is essential for effective immune responses, and its inhibitors cyclosporin A (CsA) and FK506 are used in the clinics to suppress immunity. Moreover, the kinases GSK3β and mTOR, modulated by PI 3K/Akt, can inhibit NFAT activity, suggesting a cross-talk between the calcium and growth factor signaling pathways. Both NFAT and mTOR activity have been associated with tumorigenesis. We therefore investigated the impact of calcineurin and PI-3K/mTOR inhibition in growth of human colon carcinoma cells. We show that despite the efficient inhibition of NFAT1 activity, FK506 promotes tumor growth, whereas CsA inhibits it due to a delay in cell cycle progression and induction of necroptosis. We found NFκB activation and mTORC1 activity not to be altered by CsA or FK506. Similarly, changes to mitochondrial homeostasis were equivalent upon treatment with these drugs. We further show that, in our model, NFAT1 activation is not modulated by PI3K/mTOR. We conclude that CsA slows cell cycle progression and induces necroptosis of human carcinoma cell lines in a TGFβ-, NFAT-, NFκB- and PI3K/mTOR-independent fashion. Nevertheless, our data suggest that CsA, in addition to its anti-inflammatory capacity, may target transformed colon and esophagus carcinoma cells without affecting non-transformed cells, promoting beneficial tumoristatic effects.pt_BR
dc.subjectFatores de Transcrição NFATCpt_BR
dc.subjectNFATC Transcription Factorspt_BR
dc.subjectCalcineurinapt_BR
dc.subjectCalcineurinpt_BR
dc.subjectInibidores MTORpt_BR
dc.subjectMTOR Inhibitorspt_BR
dc.subjectNeoplasiaspt_BR
dc.subjectNeoplasmspt_BR
dc.subjectCiclosporinapt_BR
dc.subjectCyclosporinept_BR
dc.subjectTacrolimopt_BR
dc.subjectTacrolimuspt_BR
dc.subjectNecroptosept_BR
dc.subjectNecroptosispt_BR
dc.subjectColopt_BR
dc.subjectColonpt_BR
dc.subjectCarcinomapt_BR
dc.titleCyclosporin A inhibits colon cancer cell growth independently of the calcineurin pathwaypt_BR
dc.TypeArticlept_BR
Appears in Collections:Artigos de Periódicos da Pesquisa Experimental e Translacional



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