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Sensitizing cancer cell lines to photodynamic therapy through inhibition of protein APE1

Grant number: 14/11870-9
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): April 01, 2015
Effective date (End): May 31, 2020
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Antonio Claudio Tedesco
Grantee:Leonardo Pereira Franchi
Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:13/50181-1 - Use of drugs containing nanocarriers with photosensitizers and/or other active compounds applied to cell therapy and treatment of central nervous system disorders, AP.TEM
Associated scholarship(s):17/14630-7 - The role of extracellular vesicles in photodynamic therapy of perihilar cholangiocarcinoma, BE.EP.PD


This project is going to use a combination of two tools of different approaches to kill cancer cell lines. The first tool is photodynamic therapy (PDT) which has the induction of cell death by apoptosis/necrosis and autophagy processes as the greater biological effect. The second approach is going to focus on the use of chemicals and siRNA to inhibit APE1 protein. APE1 is a key protein in the mechanism of base excision repair (BER), and also act as an important co-activator of transcription factors such as P53 which is a multifunctional regulator involved in proliferation and cell death. We expect that the inhibition of APE1 sensitizes cancer cell lines to treatment with photodynamic therapy. We are going to characterize the cellular and molecular events induced by the combination of these treatments. Among the cellular events we hope to evaluate the induction of cell death by apoptosis, necrosis and autophagy as well as changes in the cell cycle progression. We also expect to understand the molecular mechanisms resulting from the combined treatment aiming to characterize oxidative stress, mitochondrial stress and DNA damage. Our main hypothesis is the effective cell death induction on combination treatment (PDT + APE1 inhibition) compared to single treatments (PDT vs. APE1 inhibition). Thus these results will provide a proof of concept to support the idea that inhibition of DNA repair pathways and cell signaling can increase the efficiency of PDT in cancer treatment. (AU)

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Scientific publications (6)
(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)
DAVANZO, NATHALIA NOSSI; PELLOSI, DIOGO SILVA; FRANCHI, LEONARDO PEREIRA; TEDESCO, ANTONIO CLAUDIO. Light source is critical to induce glioblastoma cell death by photodynamic therapy using chloro-aluminiumphtalocyanine albumin-based nanoparticles. Photodiagnosis and Photodynamic Therapy, v. 19, p. 181-183, . (16/00389-3, 13/50181-1, 14/11870-9)
TEDESCO, ANTONIO CLAUDIO; SILVA, EMANOEL P. O.; JAYME, CRISTIANO C.; PIVA, HENRIQUE L.; FRANCHI, LEONARDO P.. Cholesterol-rich nanoemulsion (LDE) as a novel drug delivery system to diagnose, delineate, and treat human glioblastoma. Materials Science & Engineering C-Materials for Biological Applications, v. 123, . (12/25216-3, 18/10237-1, 13/50181-1, 14/11870-9)
FRANCHI, LEONARDO PEREIRA; BARBOSA DE FREITAS LIMA, JESSICA ELLEN; PIVA, HENRIQUE LUIS; TEDESCO, ANTONIO CLAUDIO. The redox function of apurinic/apyrimidinic endonuclease 1 as key modulator in photodynamic therapy. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, v. 211, p. 13-pg., . (17/14630-7, 13/50181-1, 14/11870-9)
JAYME, CRISTIANO CERON; DE PAULA, LEONARDO BARCELOS; REZENDE, NAYARA; CALORI, ITALO RODRIGO; FRANCHI, LEONARDO PEREIRA; TEDESCO, ANTONIO CLAUDIO. DNA polymeric films as a support for cell growth as a new material for regenerative medicine: Compatibility and applicability. Experimental Cell Research, v. 360, n. 2, p. 404-412, . (15/18684-9, 13/50181-1, 14/11870-9)
SILVA, E. P. O.; FRANCHI, L. P.; TEDESCO, A. C.. Chloro-aluminium phthalocyanine loaded in ultradeformable liposomes for photobiology studies on human glioblastoma. RSC ADVANCES, v. 6, n. 83, p. 79631-79640, . (12/25216-3, 13/50181-1, 14/11870-9)
FRANCHI, LEONARDO PEREIRA; AMANTINO, CAMILA F.; MELO, MARYANNE T.; DE LIMA MONTALDI, ANA PAULA; PRIMO, FERNANDO L.; TEDESCO, ANTONIO CLAUDIO. In vitro effects of photodynamic therapy induced by chloroaluminum phthalocyanine nanoemulsion. Photodiagnosis and Photodynamic Therapy, v. 16, p. 100-105, . (13/50181-1, 14/11870-9)

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