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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Distinct photo-oxidation-induced cell death pathways lead to selective killing of human breast cancer cells

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Dos Santos, Ancely F. [1] ; Inague, Alex [1] ; Arini, Gabriel S. [1] ; Terra, Leticia F. [1] ; Wailemann, Rosangela A. M. [1] ; Pimentel, Andre C. [1] ; Yoshinaga, Marcos Y. [1] ; Silva, Ricardo R. [2] ; Severino, Divinomar [1] ; de Almeida, Daria Raquel Q. [1] ; Gomes, Vinicius M. [1] ; Bruni-Cardoso, Alexandre [1] ; Terra, Walter R. [1] ; Miyamoto, Sayuri [1] ; Baptista, Mauricio S. [1] ; Labriola, Leticia [1]
Total Authors: 16
[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508000 Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto - Brazil
Total Affiliations: 2
Document type: Journal article
Source: CELL DEATH & DISEASE; v. 11, n. 12 DEC 14 2020.
Web of Science Citations: 0

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. (AU)

FAPESP's process: 19/09517-2 - Evaluation of the relationship between energy fluence variation and cell death pathways induced by photodynamic therapy with methylene blue in breast tumors
Grantee:Gabriel Santos Arini
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 17/13804-1 - Mechanisms of detoxification and repair of oxidized biological membranes involving the action of the enzyme peroxiredoxin 6
Grantee:Alex Inague
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 19/05026-4 - Development of a computational platform extensible and modular for analysis of metabolomics and metagenomics experiments: Innovating with the discovery of new enzymatic activities and derived natural products of interest
Grantee:Ricardo Roberto da Silva
Support type: Scholarships in Brazil - Young Researchers
FAPESP's process: 16/04676-7 - Photodynamic therapy to treat breast cancer: proof of concept pre-clinical studies
Grantee:Ancély Ferreira dos Santos
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 17/23914-9 - Exploring the immunogenic potential of photodynamic therapy
Grantee:Ancély Ferreira dos Santos
Support type: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 17/18922-2 - Development of a computing platform extensible and modular for metabolomics and metagenomics analysis: innovation with the discovery of new enzymatic activities and natural products of pharmaceutical interest derived
Grantee:Ricardo Roberto da Silva
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 17/03618-6 - Unveiling HSPB1's role in prolactin-induced modulation of the unfolded protein response in type 1 Diabetes models
Grantee:Leticia Labriola
Support type: Regular Research Grants
FAPESP's process: 15/02654-3 - Multi-User Equipment approved in grant 2014/10492-0 fluorescence microscope
Grantee:Alexandre Bruni Cardoso
Support type: Multi-user Equipment Program
FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC