Skip Navigation


JAC Advance Access originally published online on June 21, 2007
Journal of Antimicrobial Chemotherapy 2007 60(3):526-534; doi:10.1093/jac/dkm219
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
60/3/526    most recent
dkm219v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (3)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Miguel, D. C.
Right arrow Articles by Uliana, S. R. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Miguel, D. C.
Right arrow Articles by Uliana, S. R. B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Tamoxifen is effective against Leishmania and induces a rapid alkalinization of parasitophorous vacuoles harbouring Leishmania (Leishmania) amazonensis amastigotes

Danilo C. Miguel1, Jenicer K. U. Yokoyama-Yasunaka1, Walter K. Andreoli2, Renato A. Mortara2 and Silvia R. B. Uliana1,*

1 Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-900 SP, Brazil 2 Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04023-062 SP, Brazil

Received 8 February 2007; returned 7 May 2007; revised 6 April 2007; accepted 24 May 2007

* Corresponding author. Tel: +55-11-30917334; Fax: +55-11-30917417; E-mail: srbulian{at}icb.usp.br

Objectives: This study was performed to investigate the activity of tamoxifen, an antioestrogen widely used in the treatment of breast cancer, against Leishmania.

Methods: Drug activity was assessed in vitro against axenically grown promastigotes and amastigotes through cell counting or by measuring the cleavage of MTT, and against intracellular amastigotes by treating infected macrophage cultures and evaluating the number of intracellular parasites. Intravacuolar pH changes induced inside parasitophorous vacuoles of Leishmania (Leishmania) amazonensis-infected macrophages were evaluated using the fluorescent probes SNAFL-calcein and Acridine Orange.

Results: Tamoxifen killed L. (L.) amazonensis promastigotes and amastigotes with 50% inhibitory concentrations (IC50) of 16.4 ± 0.2 and 11.1 ± 0.2 µM, respectively. The drug was also effective against Leishmania (Viannia) braziliensis, Leishmania (Leishmania) major, Leishmania (Leishmania) chagasi and Leishmania (Leishmania) donovani with IC50 values ranging from 9.0 to 20.2 µM. Tamoxifen induced a rapid and long-lasting alkalinization of the vacuolar environment. We also provide evidence that tamoxifen is more effective against promastigotes and amastigotes at pH 7.5 when compared with cultures at pH 4.5.

Conclusions: Tamoxifen effectively kills several Leishmania species and its activity against the parasite is increased by a modulation of the host cell intravacuolar pH induced by the drug.

Keywords: chemotherapy , pH , oestradiol , Acridine Orange , SNAFL-calcein


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Antimicrob. Agents Chemother.Home page
S. Puiac, A. Negrea, A. Richter-Dahlfors, L. Plant, and M. Rhen
Omeprazole Antagonizes Virulence and Inflammation in Salmonella enterica-Infected RAW264.7 Cells
Antimicrob. Agents Chemother., June 1, 2009; 53(6): 2402 - 2409.
[Abstract] [Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
D. C. Miguel, R. C. Zauli-Nascimento, J. K. U. Yokoyama-Yasunaka, S. Katz, C. L. Barbieri, and S. R. B. Uliana
Tamoxifen as a potential antileishmanial agent: efficacy in the treatment of Leishmania braziliensis and Leishmania chagasi infections
J. Antimicrob. Chemother., February 1, 2009; 63(2): 365 - 368.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
H. Devalapally, Z. Duan, M. V. Seiden, and M. M. Amiji
Modulation of Drug Resistance in Ovarian Adenocarcinoma by Enhancing Intracellular Ceramide Using Tamoxifen-Loaded Biodegradable Polymeric Nanoparticles
Clin. Cancer Res., May 15, 2008; 14(10): 3193 - 3203.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.