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Fluence Rate Determines PDT Efficiency in Breast Cancer Cells Displaying Different GSH Levels

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Author(s):
dos Santos, Ancely F. ; de Almeida, Daria Raquel Q. ; Terra, Leticia F. ; Wailemann, Rosangela A. M. ; Gomes, Vinicius M. ; Arini, Gabriel S. ; Ravagnani, Felipe G. ; Baptista, Mauricio S. ; Labriola, Leticia
Total Authors: 9
Document type: Journal article
Source: Photochemistry and Photobiology; v. 96, n. 3, p. 10-pg., 2019-12-17.
Abstract

Photodynamic therapy (PDT) appears as a promising alternative in the treatment of breast cancer since it can be highly effective in curing cancer while preserving normal tissue. However, predicting outcomes in PDT still constitutes a great challenge. One of the parameters that are usually empirically determined is the rate of photon flux delivered to the tissue (light fluence rate). In the present study, we intended to understand why monolayers of human cells derived from mammary adenocarcinomas (MDA-MB-231 and MCF-7) respond quite differently to fluence rates (cells were irradiated either for 6 or for 16 min) at a fixed light dose (4.5 J cm(-2)) delivered with an array of LEDs in a typical methylene blue PDT protocol. While death rates of MDA-MB-231 cells were insensitive to the fluence rate, MCF-7 cells showed a quite impressive (three times) decrease in cell death levels in the shorter irradiation protocol. Independent on cell type cell death was invariably correlated with the depletion of reduced glutathione intracellular levels and consequently with widespread redox misbalance. Our data show the potential to optimize fluence rates to provide exhaustion of the cell antioxidant responses in order to circumvent therapy resistance of breast tumors. (AU)

FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
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 Opportunities: Regular Research Grants
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 Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 16/04676-7 - Photodynamic therapy to treat breast cancer: proof of concept pre-clinical studies
Grantee:Ancély Ferreira dos Santos
Support Opportunities: Scholarships in Brazil - Post-Doctoral