Enhancement of chlorpromazine antitumor activity by Pluronics F127/L81 nanostructured system against human multidrug resistant leukemia

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: PHARMACOLOGICAL RESEARCH; v. 111, p. 102-112, SEP 2016.
• Citações Web of Science: 5

Resumo

The development of specific tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia (CML). However, chemoresistance of tumor cells to TKIs has already been described, and several mechanisms account for the multidrug resistance (MDR) phenotypes, including the over expression of P-glycoprotein (P-gp). This decreases the rate of healing and complete tumor remission. Nanotechnological tools have been studied to allow advances in this field. Poloxamers (Pluronics) have been proposed as drug carriers to improve therapeutic efficacy and decrease side effects, even in cancer therapy, due to their ability to inhibit P-gp. Antipsychotic phenothiazines have been described as potent cytotoxic drugs against several types of tumor cells in vitro. Here, we show that nanostructured micellar systems containing the phenothiazine derivative chlorpromazine (CPZ) potentiated the cytotoxicity of free CPZ and increased the selectivity against CML tumor cells, demonstrating the pharmacological potential of these poloxamer-based nanostructured systems containing CPZ in cancer therapy. (C) 2016 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 13/05099-5 - Investigação dos mecanismos de indução de morte celular por tioridazina em células tumorais: alterações em vias de sinalização celular e na expressão de proteínas da família BCL-2
• Beneficiário: Vivian Werloger Rodrigues de Moraes
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/12247-8 - Novas aplicações de fenotiazinas e paladaciclos: utilização de sistemas nanoestruturados para o estudo dos mecanismos de morte em células tumorais
• Beneficiário: Tiago Rodrigues
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/21433-7 - Sistemas nanoestruturados contendo fenotiazinas: influência sobre o metabolismo energético e mecanismos de indução de morte em células tumorais
• Beneficiário: Joyce Cristine de Mello
• Modalidade de apoio: Bolsas no Brasil - Doutorado