دورية أكاديمية
Spermidine Suppresses Oral Carcinogenesis through Autophagy Induction, DNA Damage Repair, and Oxidative Stress Reduction.
| العنوان: | Spermidine Suppresses Oral Carcinogenesis through Autophagy Induction, DNA Damage Repair, and Oxidative Stress Reduction. |
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| المؤلفون: | Coeli-Lacchini FB; Departments of Clinical Analyses, Toxicology, and Food Sciences, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte., da Silva G; Departments of Clinical Analyses, Toxicology, and Food Sciences, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte., Belentani M; Departments of Clinical Analyses, Toxicology, and Food Sciences, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte., Alves JSF; Departments of Clinical Analyses, Toxicology, and Food Sciences, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte., Ushida TR; Departments of Clinical Analyses, Toxicology, and Food Sciences, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte., Lunardelli GT; Departments of Clinical Analyses, Toxicology, and Food Sciences, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte., Garcia CB; Departments of Clinical Analyses, Toxicology, and Food Sciences, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte., Silva TA; Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Lopes NP; Biomolecular Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, Brazil., Leopoldino AM; Departments of Clinical Analyses, Toxicology, and Food Sciences, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte. Electronic address: andreiaml@usp.br. |
| المصدر: | The American journal of pathology [Am J Pathol] 2023 Dec; Vol. 193 (12), pp. 2172-2181. Date of Electronic Publication: 2023 Sep 21. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 0370502 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-2191 (Electronic) Linking ISSN: 00029440 NLM ISO Abbreviation: Am J Pathol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2011-: New York : Elsevier Original Publication: Philadelphia [etc.] American Assn. of Pathologists [etc.] |
| مواضيع طبية MeSH: | Carcinoma, Squamous Cell*/chemically induced , Carcinoma, Squamous Cell*/prevention & control , Carcinoma, Squamous Cell*/genetics , Mouth Neoplasms*/chemically induced , Mouth Neoplasms*/prevention & control , Mouth Neoplasms*/genetics , Tongue Neoplasms*/pathology , Head and Neck Neoplasms*, Humans ; Mice ; Animals ; Spermidine/adverse effects ; 4-Nitroquinoline-1-oxide/toxicity ; Carcinogenesis/pathology ; Carcinogens ; Squamous Cell Carcinoma of Head and Neck ; DNA Damage ; DNA Repair ; Oxidative Stress ; Ceramides |
| مستخلص: | Autophagy 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. Competing Interests: Disclosure Statement None declared. (Copyright © 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.) |
| المشرفين على المادة: | U87FK77H25 (Spermidine) 56-57-5 (4-Nitroquinoline-1-oxide) 0 (Carcinogens) 0 (Ceramides) |
| تواريخ الأحداث: | Date Created: 20230923 Date Completed: 20231120 Latest Revision: 20231120 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.ajpath.2023.09.005 |
| PMID: | 37741450 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1525-2191 |
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| DOI: | 10.1016/j.ajpath.2023.09.005 |