Korean J Parasitol.  2016 Feb;54(1):9-14. 10.3347/kjp.2016.54.1.9.

Tamoxifen Induces Apoptosis of Leishmania major Promastigotes in Vitro

Affiliations
  • 1School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR. Iran.
  • 2Department of Medical Parasitology, School of Medicine, Kashan University of Medical Sciences, Kashan, IR. Iran. adoroudgar@gmail.com
  • 3Department of Pathology and Histology, School of Medicine, Kashan University of Medical Sciences, Kashan, IR. Iran.

Abstract

Tamoxifen is an antagonist of the estrogen receptor and currently used for the treatment of breast cancer. The current treatment of cutaneous leishmaniasis with pentavalent antimony compounds is not satisfactory. Therefore, in this study, due to its antileishmanial activity, effects of tamoxifen on the growth of promastigotes and amastigotes of Leishmania major Iranian strain were evaluated in vitro. Promastigotes and amastigotes were treated with different concentrations (1, 5, 10, 20, and 50 µg/ml) and time periods (24, 48, and 72 hr) of tamoxifen. After tamoxifen treatment, MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5 biphenyl tetrazolium bromide assay) was used to determine the percentage of live parasites and Graph Pad Prism software to calculate IC50. Flow cytometry was applied to investigate the induction of tamoxifen-induced apoptosis in promastigotes. The half maximal inhibitory concentration (IC50) of tamoxifen on promastigotes was 2.6 µg/ml after 24 hr treatment. Flow cytometry analysis showed that tamoxifen induced early and late apoptosis in Leishmania promastigotes. While after 48 hr in control group the apoptosis was 2.0%, the 50 µg/L concentration of tamoxifen increased it to 59.7%. Based on the in vitro antileishmanial effect, tamoxifen might be used for leishmaniasis treatment; however, further researches on in vivo effects of tamoxifen in animal models are needed.

Keyword

Leishmania major; amastigote; promastigote; apoptosis; glucantime; tamoxifen

MeSH Terms

Animals
Antiprotozoal Agents/pharmacology/therapeutic use
Apoptosis/*drug effects
Cells, Cultured
Inhibitory Concentration 50
Leishmania major/*drug effects
Leishmaniasis, Cutaneous/drug therapy
Macrophages/parasitology
Mice
Tamoxifen/*pharmacology/therapeutic use
Antiprotozoal Agents
Tamoxifen
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