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Protein p53 modulation of autophagic cell death induced by photodynamic therapy

Grant number: 14/18123-4
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2015
Effective date (End): June 30, 2016
Field of knowledge:Biological Sciences - Biochemistry
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Mauricio da Silva Baptista
Grantee:Aline Bianca de Paiva Abrantes
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:12/50680-5 - Photosensitization in life sciences, AP.TEM

Abstract

Photodynamic Therapy (PDT) is an alternative treatment modality for cancer. PDT involves the activation of a photosensitizer (FS) using visible light and molecular oxygen to induce tumor cell killing, vascular destruction and immune system activation. PDT may induce either non-programmed cell death (necrosis) or programmed cell death type 1 (apoptosis) and type 2 (autophagic cell death). The autophagy itself is a eukaryotic pathway through which cell degrades and recycles damaged macromolecules and organelles. In a recent research performed in the Laboratório de Processos Fotoinduzidos e Interfaces, IQ-USP, it has been identified that the interruption of autophagic flux, as a result of oxidative damage in mitochondria and lysosomes by PDT, drives cell death with autophagic characteristics. This is interesting because tumor cells often have defects in the apoptosis pathway. The tumor suppressor protein p53 is involved in countless number of cellular processes, including apoptosis and autophagy. We believe that the p53 expression level must perform an important role in cell response to PDT. Thereby, the present project aims find out if the p53 protein modulates the autophagic cell death induced by PDT, and also identify potential targets involved in the death process. For this, we will use cell lines HEK293 with gene silencing of p53 (about 50-90%) and the respective cell control; the FS methylene blue and 1,9-dimethyl-methylene blue, and red LED light (630 nm). After PDT in vitro, we will evaluate the photocytotoxicity, the photoactivated cell death mechanisms, the cell redox balance and some protein level changes in autophagic flux; trying to relate the PDT efficiency to the type of cell death triggered and the expression level of p53. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ABRANTES, ALINE B. DE P.; DIAS, GUSTAVO C.; SOUZA-PINTO, NADJA C.; BAPTISTA, MAURICIO S. p53-Dependent and p53-Independent Responses of Cells Challenged by Photosensitization. Photochemistry and Photobiology, v. 95, n. 1, p. 355-363, JAN 2019. Web of Science Citations: 0.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.