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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The balance between NRF2/GSH antioxidant mediated pathway and DNA repair modulates cisplatin resistance in lung cancer cells

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Silva, Matheus Molina [1] ; Reily Rocha, Clarissa Ribeiro [1, 2] ; Kinker, Gabriela Sarti [3] ; Pelegrini, Alessandra Luiza [1] ; Martins Menck, Carlos Frederico [1]
Total Authors: 5
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo, SP - Brazil
[2] Univ Fed Sao Paulo, Dept Expt & Clin Oncol, Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Inst Biosci, Dept Physiol, Sao Paulo, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 9, NOV 27 2019.
Web of Science Citations: 0

Lung cancer patients face a dismal prognosis mainly due to the low efficacy of current available treatments. Cisplatin is the first-line chemotherapy treatment for those patients, however, resistance to this drug is a common and yet not fully understood phenomenon. Aiming to shed new light into this puzzle, we used established normal and malignant lung cell lines displaying different sensitivity towards cisplatin treatment. We observed a negative correlation between cell viability and DNA damage induction upon cisplatin treatment. Interestingly, drug sensitivity in those cell lines was not due to either difference on DNA repair capacity, or in the amount of membrane ion channel commonly used for cisplatin uptake. Also, we noted that glutathione intracellular levels, and expression and activity of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) were determinant for cisplatin cytotoxicity. Remarkably, analysis of gene expression in non-small cell lung cancer patients of the TCGA data bank revealed that there is a significant lower overall survival rate in the subset of patients bearing tumors with unbalanced levels of NRF2/KEAP1 and, as consequence, increased expression of NRF2 target genes. Thus, the results indicate that NRF2 and glutathione levels figure as important cisplatin resistance biomarkers in lung cancer. (AU)

FAPESP's process: 14/15982-6 - Consequences of repair deficiencies in damaged genome
Grantee:Carlos Frederico Martins Menck
Support type: Research Projects - Thematic Grants
FAPESP's process: 15/15184-5 - Characterization of lung cancer cell lines for resistance to cisplatin
Grantee:Matheus Molina Silva
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
Grantee:Mayana Zatz
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 17/24217-0 - Mechanisms of tumor resistance to cisplatin: DNA lesions processing and circadian cycle effect
Grantee:Matheus Molina Silva
Support type: Scholarships in Brazil - Doctorate (Direct)