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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.)

Methylene blue photodynamic therapy induces selective and massive cell death in human breast cancer cells

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Author(s):
dos Santos, Ancely F. ; Terra, Leticia F. ; Wailemann, Rosangela A. M. ; Oliveira, Talita C. ; Gomes, Vinicius de Morais ; Mineiro, Marcela Franco ; Meotti, Flavia Carla ; Bruni-Cardoso, Alexandre ; Baptista, Mauricio S. ; Labriola, Leticia
Total Authors: 10
Document type: Journal article
Source: BMC CANCER; v. 17, MAR 15 2017.
Web of Science Citations: 19
Abstract

Background: Breast cancer is the main cause of mortality among women. The disease presents high recurrence mainly due to incomplete efficacy of primary treatment in killing all cancer cells. Photodynamic therapy (PDT), an approach that causes tissue destruction by visible light in the presence of a photosensitizer (Ps) and oxygen, appears as a promising alternative therapy that could be used adjunct to chemotherapy and surgery for curing cancer. However, the efficacy of PDT to treat breast tumours as well as the molecular mechanisms that lead to cell death remain unclear. Methods: In this study, we assessed the cell-killing potential of PDT using methylene blue (MB-PDT) in three breast epithelial cell lines that represent non-malignant conditions and different molecular subtypes of breast tumours. Cells were incubated in the absence or presence of MB and irradiated or not at 640 nm with 4.5 J/cm(2). We used a combination of imaging and biochemistry approaches to assess the involvement of classical autophagic and apoptotic pathways in mediating the cell-deletion induced by MB-PDT. The role of these pathways was investigated using specific inhibitors, activators and gene silencing. Results: We observed that MB-PDT differentially induces massive cell death of tumour cells. Non-malignant cells were significantly more resistant to the therapy compared to malignant cells. Morphological and biochemical analysis of dying cells pointed to alternative mechanisms rather than classical apoptosis. MB-PDT-induced autophagy modulated cell viability depending on the cell model used. However, impairment of one of these pathways did not prevent the fatal destination of MB-PDT treated cells. Additionally, when using a physiological 3D culture model that recapitulates relevant features of normal and tumorous breast tissue morphology, we found that MB-PDT differential action in killing tumour cells was even higher than what was detected in 2D cultures. Conclusions: Finally, our observations underscore the potential of MB-PDT as a highly efficient strategy which could use as a powerful adjunct therapy to surgery of breast tumours, and possibly other types of tumours, to safely increase the eradication rate of microscopic residual disease and thus minimizing the chance of both local and metastatic recurrence. (AU)

FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 12/16785-4 - Unvealing the signaling pathways involved in the cytotoxic effects of photodynamic therapy in human breast cancer cells
Grantee:Ancély Ferreira dos Santos
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 13/07029-4 - Unveiling the role of HSP25/27 in Prolactin-induced cytoprotection in pancreatic beta cells
Grantee:Leticia Labriola
Support type: Regular Research Grants
FAPESP's process: 12/50680-5 - Photosensitization in life sciences
Grantee:Mauricio da Silva Baptista
Support type: Research Projects - Thematic Grants