Journal Article

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

Labriola, Leticia, Baptista, Maurício S., Terra, Letícia F., Gomes, Vinícius de Morais, Bruni-Cardoso, Alexandre, Wailemann, Rosangela A. M., Oliveira, Talita C., dos Santos, Ancély F., Mineiro, Marcela Franco, Meotti, Flávia Carla

2017

Overview

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.

• Publisher: BioMed Central,Springer Nature B.V
• Subject: Adenocarcinoma / Animal models / Apoptosis / Atmosphere / Autophagy / Bcl protein / Bcl-2 protein / Biomedical and Life Sciences / Biomedicine / Breast cancer / Breast Neoplasms - drug therapy / Breast Neoplasms - metabolism / Cancer Research / Cancer therapies / Caspase / Caspase-3 / Caspases - metabolism / Cell and molecular biology / Cell culture / Cell death / Cell Line, Tumor / Cell Survival - drug effects / Chemotherapy / Cholera / Deoxyribonucleic acid / Disease / DNA / Epidermal growth factor / Eradication / Female / Gene expression / Gene Expression Regulation, Neoplastic - drug effects / Health Promotion and Disease Prevention / Humans / Light / Mammary gland / MCF-7 Cells / Medicine/Public Health / Metastases / Metastasis / Methylene Blue - administration & dosage / Methylene Blue - pharmacology / Morphogenesis / Oncology / Osteosarcoma cells / Phenols / Photochemotherapy - methods / Photodynamic therapy / Photosensitizing Agents - administration & dosage / Photosensitizing Agents - pharmacology / Radiation therapy / Research Article / Signal Transduction / Studies / Surgery / Surgical Oncology / Toxicity / Tumors