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Evaluation of antitumor effects of new antineoplastic phospholipids analogous an inhibitor of the enzyme CtP: phosphoethanolamine citidililtransferase in non-small cell lung cancer

Grant number: 14/07341-0
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): October 01, 2014
Effective date (End): September 30, 2015
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Jose Alexandre Marzagão Barbuto
Grantee:Adilson Kleber Ferreira
Supervisor abroad: Frank A.E. Kruyt
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : University of Groningen, Netherlands  
Associated to the scholarship:13/05396-0 - Rational desing and development of new prototypes derived of antitumor phospholipids as potential inhibitors of the enzime CTP:phosphoethanolamine citidililtransferase and antitumor agents in non-small cell lung cancer, BP.PD

Abstract

Non-small cell lung cancer (NSCLC) is therapeutically limited and despite the successful use of small molecule inhibitors there are many resistant patients to current chemotherapeutics, and this remains a major problem in the treatment of advanced disease. In this regard, it is of utmost a development of new useful compounds, efficient and selective that possibility the treatment of patients with lung cancer. An interesting and novel class of agents is the antineoplastic phospholipids that target the cell membrane by affecting its turnover leading to apoptosis induction with a highselectivity for tumor cells. Our group is engaged in the development of new CTP:phosphoethanolamine cytidylyltransferase inhibitors derivatives of antineoplastic phospholipids as novel and possible better antitumor agents. CTP:phosphoethanolamine cytidylyltransferase catalyzes a crucial step in phosphatidylethanolamine synthesis, known as the Kennedy pathway, and uses phophoethanolamine as a substrate. Inhibition of this enzyme results in cell cycle arrest and a topological impairment of the transmembrane protein domains, particularly those in mitochondria, lead to induction of apoptosis. Of note, enzymeinhibition affects the cellular bioenergetics and together with impaired lipids signaling is thought to trigger apoptosis. In the current study we will elucidate the more precise antitumor mechanism and apoptosis activation induced by antineoplasticphospholipids-analogous in NSCLC cell lines. In addition, an establish orthotopic mice model with A549-luc cells will be employed to study efficacy of the novel agents. (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)
TEIXEIRA, SARAH FERNANDES; DE AZEVEDO, RICARDO ALEXANDRE; SILVA, ARTHUR CARVALHO; BRAGA, RODOLPHO CAMPOS; JORGE, SALOMAO DORIA; MARZAGAO BARBUTO, JOSE ALEXANDRE; ANDRADE, CAROLINA HORTA; FERREIRA, ADILSON KLEBER. Evaluation of cytotoxic effect of the combination of a pyridinyl carboxamide derivative and oxaliplatin on NCI-H1299 human non-small cell lung carcinoma cells. BIOMEDICINE & PHARMACOTHERAPY, v. 84, p. 1019-1028, DEC 2016. Web of Science Citations: 1.
FERREIRA, ADILSON KLEBER; MESQUITA PASQUALOTO, KERLY FERNANDA; KRUYT, FRANK A. E.; PALACE-BERL, FANNY; AZEVEDO, RICARDO ALEXANDRE; TURRA, KELY MEDEIROS; RODRIGUES, CECILIA PESSOA; FRANCO FERREIRA, ANA CAROLINA; CLAVIJO SALOMON, MARIA ALEJANDRA; DE SA JUNIOR, PAULO LUIZ; FARIAS, CAMYLA FERNANDES; FIGUEIREDO, CARLOS ROGERIO; TAVARES, LEOBERTO COSTA; MARZAGDO BARBUTO, JOSE ALEXANDRE; JORGE, SALOMAO DORIA. BFD-22 a new potential inhibitor of BRAF inhibits the metastasis of B16F10 melanoma cells and simultaneously increased the tumor immunogenicity. Toxicology and Applied Pharmacology, v. 295, p. 56-67, MAR 15 2016. Web of Science Citations: 6.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.
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