Banca de DEFESA: DUANE GISCHEWSKI PEREIRA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : DUANE GISCHEWSKI PEREIRA
DATE: 23/02/2021
TIME: 14:00
LOCAL: meet.google.com/wca-uybq-aym
TITLE:

EVALUATION OF THE SYNERGIC EFFECT BETWEEN DIGOXIN AND CISPLATIN ON SIGNALING AND CELL STRESS

KEY WORDS:

digoxin, cisplatin, combined treatment, Src, oxidative stress

PAGES: 82
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Cardiotonic steroids have been used as cardiac drugs for over 200 years and currently several studies have shown interesting anti-tumor effects with cardiotonic steroids for a number of cell cultures. Cisplatin has played a crucial role in chemotherapy and anticancer treatments for over 30 years. However, treatment with cisplatin can cause serious side effects such as myelosuppression, ototoxicity and nephrotoxicity, in addition to the cellular resistance processes already described in prolonged use of the drug. Studies previously published by our research group have shown a potent synergistic antitumor effect between 1nM digoxin and 1µM cisplatin in cervical cancer (HeLa) cells, and elucidate a possible signaling pathway that would be triggering the antitumor process, where the effect of combined treatment on Na, K-ATPase activity and expression and Src involvement was demonstrated. The aim of the present work is to demonstrate the effect of combined treatment between digoxin and cisplatin on Src activation, through protein expression assays and the effect of combined treatment on oxidative stress parameters in HeLa cells. In addition to demonstrating the effect of treatment on other cell lines, tumor and normal. Combination treatment has been shown to increase phosphorylated Src expression in the activation residue (Tyr416), proving Src involvement in its cytotoxic effect. Analyzing the parameters of oxidative stress, we observed a significant reduction in cellular antioxidant defense mechanisms, SOD activity and GSH content and an increase in 24 hours in H₂O₂ content, confirming the increased cellular oxidative stress across the combined treatment. In addition, the levels of lipid peroxidation and lipid droplet formation were evaluated, where an increase of these parameters was observed after 48 hours of treatment, which is commonly described in cases of oxidative stress. Compared to other cell lines tested, A549 (lung cancer epithelial cells) and WI-38 (normal human fibroblast cells), the combined treatment did not have the ability to significantly alter cell viability compared to control. Our experiments suggest that the antitumor effect of synergistic treatment between digoxin and cisplatin in HeLa cells seems to be correlated with increased in the oxidative stress in this cell type by Na, K-ATPase / Src / ROS activation which in turn could culminating in different cellular effects such as signaling, antiproliferative and apoptotic effects.

BANKING MEMBERS:
Presidente - 1716846 - VANESSA FARIA CORTES
Interna - 1692875 - VALERIA ERNESTANIA CHAVES
Externo ao Programa - 1084423 - RAFAEL GONCALVES TEIXEIRA NETO
Externo à Instituição - MARCUS FERNANDES DE OLIVEIRA - UFRJ
Externo à Instituição - VICTOR DO VALLE PEREIRA MIDLEJ - Fiocruz - RJ