title: Tamoxifen Induces Apoptosis of Leishmania major Promastigotes in Vitro.
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.
authors.affiliation: School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR. Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Doroodgar
authors.affiliation: Department of Medical Parasitology, School of Medicine, Kashan University of Medical Sciences, Kashan, IR. Iran.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Delavari
authors.affiliation: School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR. Iran.
authors.forename: Moein
authors.initials: M
authors.lastname: Doroodgar
authors.affiliation: Department of Medical Parasitology, School of Medicine, Kashan University of Medical Sciences, Kashan, IR. Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Abbasi
authors.affiliation: Department of Pathology and Histology, School of Medicine, Kashan University of Medical Sciences, Kashan, IR. Iran.
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Taherian
authors.affiliation: Department of Medical Parasitology, School of Medicine, Kashan University of Medical Sciences, Kashan, IR. Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Doroodgar
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D020128:Inhibitory Concentration 50; D018320:Leishmania major / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000981:Antiprotozoal Agents; D013629:Tamoxifen
keywords: Leishmania major; amastigote; apoptosis; glucantime; promastigote; tamoxifen