Journal
PHARMACOLOGICAL RESEARCH
Volume 111, Issue -, Pages 102-112Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2016.05.032
Keywords
Cancer therapy; Leukemia; Nanostructured systems; Multidrug resistance; Poloxamers; Phenothiazines
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Funding
- Brazilian agency FAPESP [2011/21433-7, 2012/12247-8, 2013/05099-5]
- Brazilian agency CNPq [301239/2012-6]
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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.
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