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Melatonin enhances cell death and suppresses the metastatic capacity of ovarian cancer cells by attenuating the signaling of multiple kinases.
Cucielo, Maira Smaniotto; Freire, Paula Paccielli; Emílio-Silva, Maycon Tavares; Romagnoli, Graziela Gorete; Carvalho, Robson Francisco; Kaneno, Ramon; Hiruma-Lima, Clélia Akiko; Delella, Flávia Karina; Reiter, Russel J; Chuffa, Luiz Gustavo de Almeida.
Afiliación
  • Cucielo MS; Department of Structural and Functional Biology, Institute of Biosciences, UNESP - Sao Paulo State University, Botucatu 18618-689 São Paulo, Brazil.
  • Freire PP; Department of Immunology, Institute of Biomedical Sciences, USP - University of São Paulo, São Paulo, Brazil.
  • Emílio-Silva MT; Department of Structural and Functional Biology, Institute of Biosciences, UNESP - Sao Paulo State University, Botucatu 18618-689 São Paulo, Brazil.
  • Romagnoli GG; Department of Health Science, Oeste Paulista University - UNOESTE, Jaú, São Paulo, Brazil.
  • Carvalho RF; Department of Structural and Functional Biology, Institute of Biosciences, UNESP - Sao Paulo State University, Botucatu 18618-689 São Paulo, Brazil.
  • Kaneno R; Department of Structural and Functional Biology, Institute of Biosciences, UNESP - Sao Paulo State University, Botucatu 18618-689 São Paulo, Brazil.
  • Hiruma-Lima CA; Department of Structural and Functional Biology, Institute of Biosciences, UNESP - Sao Paulo State University, Botucatu 18618-689 São Paulo, Brazil.
  • Delella FK; Department of Structural and Functional Biology, Institute of Biosciences, UNESP - Sao Paulo State University, Botucatu 18618-689 São Paulo, Brazil.
  • Reiter RJ; Departament of Cell Systems and Anatomy, UT Health, San Antonio, TX 782229, USA.
  • Chuffa LGA; Department of Structural and Functional Biology, Institute of Biosciences, UNESP - Sao Paulo State University, Botucatu 18618-689 São Paulo, Brazil. Electronic address: luiz-gustavo.chuffa@unesp.br.
Pathol Res Pract ; 248: 154637, 2023 Aug.
Article en En | MEDLINE | ID: mdl-37356221
BACKGROUND: Ovarian cancer is a highly aggressive disease that is frequently diagnosed in advanced stages. Melatonin, with its numerous antitumor properties, holds great promise in cancer treatment. Herein, we investigated the effects of melatonin on apoptosis, cell migration, and kinase levels in human ovarian carcinoma SKOV-3 cells and determined whether these effects are mediated by the activation of the MT1 receptor. METHODS: SKOV-3 cells were exposed to different concentrations of melatonin based on the presence of MT1 receptor, and we also performed specific silencing of the melatonin receptor gene MTNR1A. RESULTS: Our findings revealed that melatonin reduced cell viability as shown by the MTT assay, and flow cytometry analysis showed increased rates of apoptosis and necrosis in all melatonin-treated cells. Melatonin significantly decreased the migratory and invasive capacities of the cells. Propidium iodide labeling indicated that melatonin induced cell cycle arrest by reducing DNA content in the S and G2/M phases in SKOV-3 cells. Additionally, the levels of AKT, ERK1/2, JNK, CREB, p70S6K, STAT3/5, and p38 MAP kinase involved in cell survival, proliferation, motility, and stress responses were depressed by melatonin and further reduced after MT1 knockdown. These molecules were found to be associated with lower overall survival in ovarian cancer patients. CONCLUSIONS: Melatonin had obvious oncostatic actions on ovarian cancer cells, and MT1 receptor knockdown intensified its antitumor effect. The inhibition of the MT1 receptor resulted in a substantial reduction in the migratory and invasive capacities of the cells, suggesting its potential as a therapeutic target for the treatment of ovarian cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pathol Res Pract Año: 2023 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pathol Res Pract Año: 2023 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Alemania