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Nanostructured systems containing phenothiazines: effects on bioenergetics and mechanisms of death in tumor cells

Grant number: 11/21433-7
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2012
Effective date (End): April 30, 2015
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Tiago Rodrigues
Grantee:Joyce Cristine de Mello
Home Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Multi-drug resistance (MDR) is the main problem that contributes to the antitumoral chemotherapy fail. Such resistance is related to overexpression or inactivation of genes associated to signaling in tumor cells. The most studied mechanism of MDR involves the glycoprotein P (Pgp), the product of MDR1 gene. The MDR reversion by inhibition of Pgp has been described for several chemicals, including phenothiazines, pointing to the antitumoral potential of this class of drugs. Studies involving ethylene and propylene oxides copolymers, named poloxamers, also demonstrates their inhibitory activity of Pgp besides their effects on mitochondrial respiration. Thus, the aim of this work is to investigate the alterations in mitochondrial bioenergetics and the mechanisms of cell death induced by nanostructured systems containing phenothiazines (thioridazine, trifluoperazine, and chlorpromazine) formed by poloxamers in K562 human leukemia cells and K562-Lucena, which overexpress the MDR1 gene. This study will improve the understanding of the biochemistry of the leukemia tumor cells and also it will evaluate the potential antitumoral of these nanostructured systems containing phenothiazines.

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)
DE MELLO, JOYCE C.; MORAES, VIVIAN W. R.; WATASHI, CAROLINA M.; DA SILVA, DEYSE C.; CAVALCANTI, LEIDE P.; FRANCO, MARGARETH K. K. D.; YOKAICHIYA, FABIANO; DE ARAUJO, DANIELE R.; RODRIGUES, TIAGO. Enhancement of chlorpromazine antitumor activity by Pluronics F127/L81 nanostructured system against human multidrug resistant leukemia. PHARMACOLOGICAL RESEARCH, v. 111, p. 102-112, SEP 2016. Web of Science Citations: 5.

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