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Modulation of biochemical and photochemical parallel damages: implications on pro-survival autophagy

Grant number: 18/23257-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2019
Effective date (End): November 30, 2019
Field of knowledge:Biological Sciences - Biophysics
Principal Investigator:Waleska Kerllen Martins Gardesani
Grantee:Maryana do Nascimento da Silva
Home Institution: Anhanguera Educacional S/A (AESA). São Bernardo do Campo , SP, Brazil

Abstract

Human cancer represents a significant public health problem worldwide. As a strategy to reverse this reality, the modulation of autophagy as an antitumor approach has been investigated. Depending on the context, such as tumor type and staging, both activating agents and autophagy inhibitors have antitumor action. Similarly, Photodynamic Therapy (PDT) has been highlighted as a modulator of pro-survival autophagy. By comparative analysis using human non-malignant and malignant cells, we intend to promote extrinsic cellular stresses in which pro-survival autophagy can be modulated to cell death by suppressing lysosomal function. By using technologic tools in cellular and molecular biology, we intend to modulate autophagy after treatment with the pentacyclic triterpenoids betulinic acid (BA) and oleanolic acid (OA) parallel or not to the photodamage promoted by PDT using as photosensitizers (PSs) the phenothiazine compounds methylene blue (MB) and 1,9-dimethyl-methylene blue (DMMB). Comparative analysis regarding the PDT efficiency using these PSs and according to the presence or absence of parallel mitochondrial (OA) or mitochondrial/lysosomal (BA) membrane damage may contribute to the understanding of the concept of lysosomal damage and its impact on the role of pro-survival autophagy. Thus, by expanding this model in the near future, it will be possible to subsidize new scientific developments in biotechnological innovation, in order to consolidate the public interest in promoting an improvement in the survival of cancer patients.