Unvealing the signaling pathways involved in the cytotoxic effects of photodynamic therapy in human breast cancer cells

Abstract

Breast cancer is a devastating disease with major impact on global health, where metastasis remains the main cause of death. The chance for a patient to live for more than five years after diagnosis falls from >90% for localized diseases to <20% once metastasis has occurred. Hence, the only way to improve the patient survival is preventing that cancer cells metastasize. Photodynamic therapy (PDT), which cause tissue destruction by visible light in the presence of a photosensitizing substance and oxygen, appears as a promising alternative for cancer treatment. However, the mechanisms of the cells death as well as the efficacy of PDT on mammary tumors remain unclear. Therefore, in this project we set out to study signaling pathways involved in cell death, such as apoptosis, autophagy, piropotosis and necroptosis, as possible mediators of the cytotoxic effects of PDT by using the methylene blue dye (AM), as a photosensitizer, in human breast tumor cells with different invasive properties growing in two and three dimensions. For this purpose, we intend to assess the presence of markers cell death like RIP1, RIP3, mTOR and LC3-II as well as the activities of some of the key enzymes involved in these processes such as caspase 1, 3, 8 and 9. Understanding the mechanisms behind the cytotoxic effects of PDT may lead to clarify the still unknown signaling pathways involved in the AM action in PDT as well as to the discovery of new potential biological targets for the development of additional therapies for the treatment of more aggressive breast tumors. (AU)