PT  - JOURNAL ARTICLE
AU  - Ancély F. dos Santos
AU  - Alex Inague
AU  - Gabriel S. Arini
AU  - Letícia F. Terra
AU  - Rosangela A.M. Wailemann
AU  - André C. Pimentel
AU  - Marcos Y. Yoshinaga
AU  - Ricardo R. Silva
AU  - Divinomar Severino
AU  - Daria Raquel Q. de Almeida
AU  - Vinícius M. Gomes
AU  - Alexandre Bruni-Cardoso
AU  - Walter R. Terra
AU  - Sayuri Miyamoto
AU  - Maurício S. Baptista
AU  - Leticia Labriola
TI  - Distinct photooxidation-induced cell death pathways lead to selective killing of human breast cancer cells
AID  - 10.1101/2020.06.25.170860
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.25.170860
4099  - http://biorxiv.org/content/early/2020/06/26/2020.06.25.170860.short
4100  - http://biorxiv.org/content/early/2020/06/26/2020.06.25.170860.full
AB  - Lack of effective treatments for aggressive breast cancer is still a major global health problem. We 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. Through lipidomic and biochemical approaches we demonstrated that MB-PDT efficiency and specificity relies on polyunsaturated fatty acids-enriched membranes and on the better capacity to deal with photooxidative 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 broadened the understanding of MB-PDT-induced photooxidation 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.Competing Interest StatementThe authors have declared no competing interest.