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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Leishmania is not prone to develop resistance to tamoxifen

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Author(s):
Coelho, Adriano C. [1] ; Trinconi, Cristiana T. [1] ; Senra, Luisa [1] ; Yokoyama-Yasunaka, Jenicer K. U. [1] ; Uliana, Silvia R. B. [1]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, BR-05508900 Sao Paulo, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE; v. 5, n. 3, p. 77-83, DEC 2015.
Web of Science Citations: 9
Abstract

Tamoxifen, an antineoplastic agent, is active in vitro and in vivo against the parasitic protozoa Leishmania. As part of our efforts to unravel this drug's mechanisms of action against the parasite and understand how resistance could arise, we tried to select tamoxifen-resistant Leishmania amazonensis. Three different strategies to generate tamoxifen resistant mutants were used: stepwise increase in drug concentration applied to promastigote cultures, chemical mutagenesis followed by drug selection and treatment of infected mice followed by selection of amastigotes. For amastigote selection, we employed a method with direct plating of parasites recovered from lesions into semi-solid media. Tamoxifen resistant parasites were not rescued by any of these methods. Miltefosine was used as a control in selection experiments and both stepwise selection and chemical mutagenesis allowed successful isolation of miltefosine resistant mutants. These findings are consistent with a multi-target mode of action to explain tamoxifen's leishmanicidal properties. Considering that drug resistance is a major concern in antiparasitic chemotherapy, these findings support the proposition of using tamoxifen as a partner in drug combination schemes for the treatment of leishmaniasis. (C) 2015 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology. (AU)

FAPESP's process: 11/20484-7 - Tamoxifen in the treatment of leishmaniasis: evaluation of efficacy in combination therapy schemes and study of the antileishmanial mechanism of action
Grantee:Silvia Reni Bortolin Uliana
Support type: Regular Research Grants
FAPESP's process: 12/14629-5 - Mechanisms of action and resistance to miltefosine in Leishmania spp.
Grantee:Adriano Cappellazzo Coelho
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 11/18858-6 - TAMOXIFEN AS AN ANTI-LEISHMANIAL DRUG: ACTIVITY IN COMBINED THERAPEUTIC SCHEMES AND STUDY OF THE MECHANISM OF ACTION
Grantee:Cristiana de Melo Trinconi Tronco
Support type: Scholarships in Brazil - Doctorate