Fluence Rate Determines PDT Efficiency in Breast Cancer Cells Displaying Different GSH Levels. (17th December 2019)

• Record Type: Journal Article
• Authors: dos Santos, Ancély F.; de Almeida, Daria Raquel Q.; Terra, Letícia F.; Wailemann, Rosangela A.M.; Gomes, Vinícius M.; Arini, Gabriel S.; Ravagnani, Felipe G.; Baptista, Maurício S.; Labriola, Leticia
• Other Names: Hasan Tayyaba guestEditor.; Kessel David guestEditor.; Greer Alexander guestEditor.
• Is Part Of: Photochemistry and photobiology. Volume 96:Number 3(2020)
• Page Start: 658
• Page End: 667
• Publication Date: 2019-12-17
• Subjects: Photochemistry -- Periodicals; Light -- Physiological effect -- Periodicals; 541.35
• DOI: 10.1111/php.13182
• Languages: English
• ISSNs: 0031-8655

Abstract

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. Abstract : When MB is activated using a low fluence rate, this results in GSH depletion and ROS accumulation, culminating in cell death for both cell types. However, the basal intracellular GSH content can determine the cell sensitivity in a high energy fluence rate MB‐PDT protocol. TNBC cells presents less GSH content and more susceptibility to respond to the high energy fluence rate. Unlike TNBC cells, luminal A cells display higher levels of GSH, and when submitted to MB‐PDT using high energy fluence rate, a less pro‐oxidative milieu is generated leading to lower levels of cell death.