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Role of notch pathway and HNF1 in cell death induced by HDACs inhibitors in ovarian cancer cell lines, serous and clear cells

Ovarian cancer is the leading cause of death from gynaecological malignancies due to difficulties in early detection, diagnosis and therapy of the disease. There is an urgent need for testing novel tumour markers and therapeutic agents. Histone deacetylases (HDACs) inhibitors are a new class of target anticancer agents, which block the deacetylation function, inducing cell cycle arrest, differentiation and/or apoptosis. Vorinostat is an inhibitor of class I and II HDACs and butyric acid is a small molecular weight carboxylate that belong to class I HDAC inhibitors. Our aim was to study cell and molecular alterations induced by HDACs inhibitors in ovarian cancer cell lines. Ovarian cancer cell lines used were OV-90 and OVCAR-3 (serous carcinoma), and ES-2 (clear cell carcinoma). Cell lines were exposed to butyric acid and to vorinostat and cell death (apoptosis and necrosis), was evaluated by FACS using Annexin V and 7AAD staining. Notch downstream target genes, and TP53 (mutated in serous carcinomas) and Fibronectin (FN1) genes were evaluated by RQ-PCR. We found that butyric acid was more effective to induce cell death than vorinostat, in all cell lines tested, although Vorinostat was able to induce higher levels of apoptosis in OV-90 than in other cell lines. Regarding the evaluation of Notch pathway, we observed it is activated by butyric acid in all ovarian cell lines, since Notch downstream targets HES1, HEY1 and 2 genes are more expressed after exposure to this compound. TP53 expression is slightly decreased in all cell lines after exposure to butyric acid. Interestingly, FN1 expression decreases in OV90 whereas it increases in ES2 and OVCAR3 after exposure to vorinostat. We conclude that butyric acid induces cell death in all cell lines; and the induction of apoptosis in OV90 by vorinostat may be through the downregulation of HNF1.

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Correspondence to Fernanda Silva.

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Fernanda Silva, Jacinta Serpa contributed equally to this work.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Silva, F., Serpa, J., Domingues, G. et al. Role of notch pathway and HNF1 in cell death induced by HDACs inhibitors in ovarian cancer cell lines, serous and clear cells. BMC Proc 4 (Suppl 2), P36 (2010). https://doi.org/10.1186/1753-6561-4-S2-P36

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  • DOI: https://doi.org/10.1186/1753-6561-4-S2-P36

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