Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/72538
Título: | Disruption of pH dynamics suppresses proliferation and potentiates doxorubicin cytotoxicity in breast cancer cells |
Autor(es): | Tavares-Valente, Diana Sousa, Bárbara Schmitt, Fernando Baltazar, Fátima Queirós, Odília |
Palavras-chave: | pH regulators reverse pH gradient tumor microenvironment treatment resistance |
Data: | 2021 |
Editora: | Multidisciplinary Digital Publishing Institute |
Revista: | Pharmaceutics |
Citação: | Tavares-Valente, D.; Sousa, B.; Schmitt, F.; Baltazar, F.; Queirós, O. Disruption of pH Dynamics Suppresses Proliferation and Potentiates Doxorubicin Cytotoxicity in Breast Cancer Cells. Pharmaceutics 2021, 13, 242. https://doi.org/10.3390/pharmaceutics13020242 |
Resumo(s): | The reverse pH gradient is a major feature associated with cancer cell reprogrammed metabolism. This phenotype is supported by increased activity of pH regulators like ATPases, carbonic anhydrases (CAs), monocarboxylate transporters (MCTs) and sodium–proton exchangers (NHEs) that induce an acidic tumor microenvironment, responsible for the cancer acid-resistant phenotype. In this work, we analyzed the expression of these pH regulators and explored their inhibition in breast cancer cells as a strategy to enhance the sensitivity to chemotherapy. Expression of the different pH regulators was evaluated by immunofluorescence and Western blot in two breast cancer cell lines (MDA-MB-231 and MCF-7) and by immunohistochemistry in human breast cancer tissues. Cell viability, migration and invasion were evaluated upon exposure to the pH regulator inhibitors (PRIs) concanamycin-A, cariporide, acetazolamide and cyano-4-hydroxycinnamate. Additionally, PRIs were combined with doxorubicin to analyze the effect of cell pH dynamic disruption on doxorubicin sensitivity. Both cancer cell lines expressed all pH regulators, except for MCT1 and CAXII, only expressed in MCF-7 cells. There was higher plasma membrane expression of the pH regulators in human breast cancer tissues than in normal breast epithelium. Additionally, pH regulator expression was significantly associated with different molecular subtypes of breast cancer. pH regulator inhibition decreased cancer cell aggressiveness, with a higher effect in MDA-MB-231. A synergistic inhibitory effect was observed when PRIs were combined with doxorubicin in the breast cancer cell line viability. Our results support proton dynamic disruption as a breast cancer antitumor strategy and the use of PRIs to boost the activity of conventional therapy. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/72538 |
DOI: | 10.3390/pharmaceutics13020242 |
e-ISSN: | 1999-4923 |
Versão da editora: | https://www.mdpi.com/1999-4923/13/2/242 |
Acesso: | Acesso aberto |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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pharmaceutics-13-00242-v2.pdf | 5,93 MB | Adobe PDF | Ver/Abrir |
Este trabalho está licenciado sob uma Licença Creative Commons