Leishmania is not prone to develop resistance to tamoxifen
| Autor: | Luisa Senra, Cristiana T. Trinconi, Adriano C. Coelho, Silvia R. B. Uliana, Jenicer K.U. Yokoyama-Yasunaka |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Selective Estrogen Receptor Modulators
Drug Phosphorylcholine media_common.quotation_subject Antiprotozoal Agents PBS phosphate buffered solution Drug resistance Biology Pharmacology Article lcsh:Infectious and parasitic diseases Mice Cell Line Tumor MT miltefosine transporter medicine Animals Humans Chemotherapy lcsh:RC109-216 Pharmacology (medical) Amastigote Mode of action Leishmaniasis media_common Leishmania Mice Inbred BALB C Miltefosine Dose-Response Relationship Drug TM tamoxifen biology.organism_classification medicine.disease Tamoxifen MNNG N-methyl-N-nitroso-N′-nitroguanidine Infectious Diseases Female Parasitology NBD-PC 2-(6-(7-nitrobenz-2-oxa-1 3-diazol-4-yl)amino)hexanoyl-1-hexadecanoyl-sn-glycero-3-phosphocholine Leishmania amazonensis medicine.drug |
| Zdroj: | International Journal for Parasitology: Drugs and Drug Resistance, Vol 5, Iss 3, Pp 77-83 (2015) International Journal for Parasitology: Drugs and Drug Resistance |
| ISSN: | 2211-3207 |
| DOI: | 10.1016/j.ijpddr.2015.05.006 |
| Popis: | 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 anti-parasitic chemotherapy, these findings support the proposition of using tamoxifen as a partner in drug combination schemes for the treatment of leishmaniasis. Graphical abstract Highlights • Tamoxifen is effective in the treatment of cutaneous and visceral leishmaniasis. • Resistance to tamoxifen was not found in promastigotes upon mutagenesis/selection. • Resistance to tamoxifen was not detected in amastigotes after in vivo selection. • Tamoxifen may be a good partner in drug combination schemes for leishmaniasis. |
| Databáze: | OpenAIRE |
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