Spermidine suppresses oral carcinogenesis through autophagy induction,DNA damage repair, and oxidative stress reduction

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dc.creatorFernanda Borcherscoeli-Lacchini
dc.creatorGabriel da Silva
dc.creatorMonica Belentani
dc.creatorJovelina Samara Ferreira Alves
dc.creatorTatiane Resende Ushida
dc.creatorGlauce Trevisan Lunardelli
dc.creatorCristiana Bernadelli Garcia
dc.creatorTarcília Aparecida da Silva
dc.creatorNorberto Peporine Lopes
dc.creatorAndréia Machado Leopoldino
dc.date.accessioned2025-05-20T20:30:02Z
dc.date.accessioned2025-09-09T01:09:58Z
dc.date.available2025-05-20T20:30:02Z
dc.date.issued2023-12
dc.description.sponsorshipFAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulo
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.1016/j.ajpath.2023.09.005
dc.identifier.issn1525-2191
dc.identifier.urihttps://hdl.handle.net/1843/82389
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofThe american journal of pathology
dc.rightsAcesso Restrito
dc.subjectAutophagy
dc.subjectCeramides
dc.subjectCarcinogenesis
dc.subjectOxidation
dc.subjectSpermidine
dc.subjectChloroquine
dc.subjectMouth neoplasms
dc.subjectDNA
dc.titleSpermidine suppresses oral carcinogenesis through autophagy induction,DNA damage repair, and oxidative stress reduction
dc.typeArtigo de periódico
local.citation.epage2181
local.citation.issue12
local.citation.spage2172
local.citation.volume193
local.description.resumoAutophagy has been proposed to play a dual role in cancer-as a tumor suppressor in early stages and oncogenic in late stages of tumorigenesis. This study investigated the role of autophagy in oral carcinogenesis using the model of oral squamous cell carcinoma (OSCC) induced by carcinogen 4-nitroquinoline 1-oxide (4NQO), mimicking molecular and histopathologic aspects of human OSCC. The induction of autophagy by spermidine (SPD) treatment reduced the severity of lesions and the incidence of OSCC in mice exposed to 4NQO. On the other hand, autophagy inhibition by chloroquine treatment had no protection. The comet assay indicated that SPD reduced 4NQO-induced DNA damage, likely related to the activation of DNA repair and the decrease of reactive oxygen species. As sphingolipid alterations have been reported in OSCC, sphingolipids in the tongue and plasma of animals were analyzed and plasma C16 ceramide levels were shown to increase proportionally to lesion severity, indicating its potential as a biomarker. Mice exposed to 4NQO plus SPD had lower levels of C16 ceramide than the 4NQO group, which indicated SPD's ability to prevent the 4NQO-induced carcinogenesis. Together, these data indicate that activation of autophagy has a tumor suppressor role during the early stages of oral carcinogenesis. Because of its ability to induce autophagy accompanied by reduced oxidative stress and DNA damage, SPD may have a protective action against chemically induced oral cancer.
local.identifier.orcidhttps://orcid.org/0000-0001-6568-7497
local.identifier.orcidhttps://orcid.org/0000-0002-8313-4754
local.identifier.orcidhttps://orcid.org/0000-0003-3445-8733
local.identifier.orcidhttps://orcid.org/0000-0002-8424-113X
local.identifier.orcidhttps://orcid.org/0000-0002-3161-7615
local.identifier.orcidhttps://orcid.org/0000-0003-1354-7024
local.identifier.orcidhttps://orcid.org/0000-0001-9623-7835
local.identifier.orcidhttps://orcid.org/0000-0002-8159-3658
local.publisher.countryBrasil
local.publisher.departmentFAO - DEPARTAMENTO DE CLÍNICA
local.publisher.initialsUFMG
local.url.externahttps://www.sciencedirect.com/science/article/pii/S0002944023003619?via%3Dihub

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