| Texto completo | |
| Autor(es): |
Coeli-Lacchini, Fernanda B.
;
da Silva, Gabriel
;
Belentani, Monica
;
Alves, Jovelina S. F.
;
Ushida, Tatiane R.
;
Lunardelli, Glauce T.
;
Garcia, Cristiana B.
;
Silva, Tarcilia A.
;
Lopes, Norberto P.
;
Leopoldino, Andreia M.
Número total de Autores: 10
|
| Tipo de documento: | Artigo Científico |
| Fonte: | American Journal of Pathology; v. 193, n. 12, p. 10-pg., 2023-11-17. |
| Resumo | |
Autophagy has been proposed to play a dual role in cancerdas 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 4nitroquinoline 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. (Am J Pathol 2023, 193: 2172e2181; https://doi.org/10.1016/j.ajpath.2023.09.005) (AU) | |
| Processo FAPESP: | 19/22663-8 - Seleção de candidatos a biomarcadores de câncer oral humano utilizando espectrometria de massas acopladas à cromatografia líquida de alta eficiência |
| Beneficiário: | Jovelina Samara Ferreira Alves |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 20/00101-5 - Diferentes estratégias experimentais e abordagens para o estudo de marcadores moleculares em câncer |
| Beneficiário: | Glauce Lunardelli Trevisan |
| Modalidade de apoio: | Bolsas no Brasil - Programa Capacitação - Treinamento Técnico |
| Processo FAPESP: | 16/19103-2 - SET e esfingolipídeos em câncer de cabeça e pescoço: sinalização, alvos e terapia antitumoral |
| Beneficiário: | Andréia Machado Leopoldino |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 18/17480-9 - Estudo da SET e esfingolipídeos em câncer de cabeça e pescoço: sinalização, alvos e terapia antitumoral |
| Beneficiário: | Gabriel da Silva |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |