ESCUELA DE DOCTORADO

 
Tesis Doctorales de la Universidad de Alcalá
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REDOX MODULATION BY SOD MIMICS IN RENAL CANCER: FROM ETIOLOGY TO PROGRESSION
Autor/aFeliciano Da Costa, João Guilherme
DepartamentoBiología de Sistemas
Director/aGregório Fernandes, Ana Sofía
Codirectores/asLucio Cazaña, Francisco Javier De; Oliveira , Nuno
Fecha de defensa08/01/2018
CalificaciónSobresaliente Cum Laude
ProgramaCiencias de la Salud (RD 99/2011)
Mención internacionalSi
ResumenCancer is a multistep process and oxidative stress has been pointed out to have critical roles on its initiation, promotion and progression. This thesis addresses the redox modulation afforded by the superoxide dismutase mimic (SODm) MnTnHex-2-PyP (MnP), a prototype of the Manganese(III) porphyrins (MnPs), which are catalytical polyfunctional antioxidants with the ability to modulate different cellular redox pathways. Two different renal cell models were used to address initiation and progression cellular events. Firstly, the role of MnP on the toxicity of non-tumor renal cells exposed to the ochratoxin A (OTA) was evaluated. The MnP protected cells from the OTA-induced cytotoxicity. In addition, it modulated the intracellular reactive oxygen species (ROS) levels and decreased the percentage of cells in apoptosis when compared with cells exposed only to OTA. The role of the MnP in renal cancer progression was subsequently studied in a human renal cancer cell model. MnP decreased the cell viability of human 786-O cells and also induced an increase in intracellular ROS. Notably, low concentrations of the MnP significantly decreased the chemotactic migration of the 786-O cells. This study contributed to clarify the role of oxidative stress in OTA-induced toxicity. In addition, this work revealed the potential of MnTnHex-2-PyP in renal cancer treatment, by decreasing cancer cells viability and migration. Overall, this MnP protected non-tumor cells from the toxic effects induced by OTA, while it had a beneficial effect against renal cancer cells. The results obtained herein reinforce the multiple potential applications of MnPs and warrant further studies towards their therapeutic use.