Docosahexaenoic acid promotes cell cycle arrest and decreases proliferation through WNT/β-catenin modulation in colorectal cancer cells exposed to γ-radiation
| Autor: | Waldemir Fernandes de Souza, Lilian G. Bastos, José Andrés Morgado-Díaz, Murilo Ramos Rocha, Annie Cristhine Moraes Sousa-Squiavinato, Leonardo Borges Murad, Wallace Martins de Araújo, Pedro Barcellos-de-Souza, Perôny da Silva Nogueira, Julio Cesar Madureira de-Freitas-Junior |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell signaling Cell cycle checkpoint Chemistry Clinical Biochemistry Wnt signaling pathway General Medicine Cell cycle Biochemistry 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Apoptosis Docosahexaenoic acid 030220 oncology & carcinogenesis Catenin Cancer research Molecular Medicine Viability assay |
| Zdroj: | BioFactors. 45:24-34 |
| ISSN: | 0951-6433 |
| Popis: | The effects of radiation are known to be potentiated by N-3 polyunsaturated fatty acids, which modulate several signaling pathways, but the molecular mechanisms through which these fatty acids enhance the anticancer effects of irradiation in colorectal cancer (CRC) treatment remain poorly elucidated. Here, we aimed to ascertain whether the fatty acid docosahexaenoic acid (DHA) exerts a modulating effect on the response elicited by radiation treatment (RT). Two CRC cell lines, Caco-2 and HT-29, were exposed to RT, DHA, or both (DHA + RT) for various times, and then cell viability, proliferation, and clonogenicity were assessed. Moreover, cell cycle, apoptosis, and necrosis were analyzed using flow cytometry, and the involvement of WNT/β-catenin signaling was investigated by immunofluorescence to determine nuclear β-catenin, GSK3β phosphorylation status, and TCF/LEF-activity reporter. DHA and RT applied separately diminished the viability of both HT-29 and Caco-2 cells, and DHA + RT caused a further reduction in proliferation mainly in HT-29 cells, particularly in terms of colony formation. Concomitantly, our results verified cell cycle arrest in G0/G1 phase, a reduction of cyclin D1 expression, and a decrease in GSK3β phosphorylation after the combined treatment. Furthermore, immunofluorescence quantification revealed that nuclear β-catenin was increased in RT-exposed cells, but this effect was abrogated in cells exposed to DHA + RT, and the results of TCF/LEF-activity assays confirmed that DHA attenuated the increase in nuclear β-catenin activity induced by irradiation. Our finding shows that DHA applied in combination with RT enhanced the antitumor effects of irradiation on CRC cells, and that the underlying mechanism involved the WNT/β-catenin pathway. © 2018 BioFactors, 45(1):24-34, 2019. |
| Databáze: | OpenAIRE |
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