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In vitro and in vivo study of new compounds: with target-specific (hnRNP K) or action in the mitochondria for use as antitumor oral carcinoma or as cytoprotective in non-tumor cell

Grant number: 13/01355-7
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): May 01, 2013
Effective date (End): May 31, 2017
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Andréia Machado Leopoldino
Grantee:Renata Nishida Goto
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

In Brazil, the cancer appears as the second cause of mortality, second only to cardiovascular disease. The estimates for cancer of the oral cavity is about 9990 new cases in men and women in 4180, to Brazil in 2012. These values correspond to an estimated risk of 10 new cases per 100 000 men and 4 per 100 thousand women. Advances in understanding the biology of head and neck cancers have opened new directions in science. The research is being directed toward the development of therapies to specific molecular targets that are useful in the prediction of treatment or in the selection of patients who may respond to a given therapy based on molecular tumor molecular alterations. The hnRNP K protein recently identified as overexpressed in cancer of the head and neck, especially on the tongue and larynx, represents a new and attractive therapeutic target for this type of cancer, and may planning drug candidates targeting this protein enrich the therapeutic armamentarium against the disease, with the use of pharmacological therapies more effective and less aggressive, not only in head and neck cancer, but possibly in breast cancer and colorectal cancer, since there is also evidence of the involvement of hnRNP K in the progression of disease. The mitochondria of cancer cells has also been studied, as there are differences between the mitochondria of normal cells and cancer cells. The differences genetic, molecular and biochemical factors may be causal or contribute to cancer development. Based on these data we selected four compounds, two specific target (hnRNP K) and 2 compounds that act on mitochondria to study the effects in vitro and in vivo cell viability and assess the antitumor potential as cytoprotective or with potential application as a new drug. In this work are used human oral carcinoma cell lines, primary culture of human fibroblasts and human keratinocyte line of immortalized non-tumoral for analyzing the effects of different compounds screened. The methods comprise different techniques for determination of cell viability type of cell death, genotoxicity, molecular response with increased or phosphorylation of proteins, oxidative stress response, etc.. It is intended in order to have the design characteristics of the compounds as antitumor or cytoprotective and Preliminary pharmacokinetic results (only if the compounds have proposed the effect). (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)
GOTO, RENATA NISHIDA; SOBRAL, LAYS MARTIN; STRINGHETTA-PADOVANI, KARINA; GARCIA, CRISTIANA B.; DA SILVA, GABRIEL; VITEK, MICHAEL P.; LEOPOLDINO, ANDREIA MACHADO. Synergic effect of OP449 and FTY720 on oral squamous cell carcinoma. European Journal of Pharmacology, v. 882, SEP 5 2020. Web of Science Citations: 0.
GOTO, RENATA NISHIDA; SOBRAL, LAYS MARTIN; SOUSA, LUCAS OLIVEIRA; GARCIA, CRISTIANA BERNADELLI; LOPES, NORBERTO PEPORINE; MARIN-PRIDA, JAVIER; OCHOA-RODRIGUEZ, ESTAEL; VERDECIA-REYES, YAMILA; LAZARO PARDO-ANDREU, GILBERTO; CURTI, CARLOS; LEOPOLDINO, ANDREIA MACHADO. Anti-cancer activity of a new dihydropyridine derivative, VdiE-2N, in head and neck squamous cell carcinoma. European Journal of Pharmacology, v. 819, p. 198-206, JAN 15 2018. Web of Science Citations: 13.
ALMEIDA, LUCIANA O.; GOTO, RENATA N.; NETO, MARINALDO P. C.; SOUSA, LUCAS O.; CURTI, CARLOS; LEOPOLDINO, ANDREIA M. SET overexpression in HEK293 cells regulates mitochondrial uncoupling proteins levels within a mitochondrial fission/reduced autophagic flux scenario. Biochemical and Biophysical Research Communications, v. 458, n. 2, p. 300-306, MAR 6 2015. Web of Science Citations: 5.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
GOTO, Renata Nishida. Studies in vitro and in vivo novel compounds: with target-specific (hnRNP K and SET) or the mitochondrion action for use as antitumor in oral carcinoma cell or as cytoprotection in non-tumor. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto Ribeirão Preto.

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