| Autor: |
Ancély F. Dos Santos, Alex Inague, Gabriel S. Arini, Letícia F. Terra, Rosangela A. M. Wailemann, André C. Pimentel, Marcos Y. Yoshinaga, Ricardo R. Silva, Divinomar Severino, Daria Raquel Q. de Almeida, Vinícius M. Gomes, Alexandre Bruni-Cardoso, Walter R. Terra, Sayuri Miyamoto, Maurício S. Baptista, Leticia Labriola |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Cell Death and Disease, Vol 11, Iss 12, Pp 1-12 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2041-4889 |
| DOI: |
10.1038/s41419-020-03275-2 |
| Popis: |
Abstract Lack of effective treatments for aggressive breast cancer is still a major global health problem. We have previously reported that photodynamic therapy using methylene blue as photosensitizer (MB-PDT) massively kills metastatic human breast cancer, marginally affecting healthy cells. In this study, we aimed to unveil the molecular mechanisms behind MB-PDT effectiveness and specificity towards tumor cells. Through lipidomics and biochemical approaches, we demonstrated that MB-PDT efficiency and specificity rely on polyunsaturated fatty acid-enriched membranes and on the better capacity to deal with photo-oxidative damage displayed by non-tumorigenic cells. We found out that, in tumorigenic cells, lysosome membrane permeabilization is accompanied by ferroptosis and/or necroptosis. Our results also pointed at a cross-talk between lysosome-dependent cell death (LDCD) and necroptosis induction after photo-oxidation, and contributed to broaden the understanding of MB-PDT-induced mechanisms and specificity in breast cancer cells. Therefore, we demonstrated that efficient approaches could be designed on the basis of lipid composition and metabolic features for hard-to-treat cancers. The results further reinforce MB-PDT as a therapeutic strategy for highly aggressive human breast cancer cells. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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