Tamoxifen Induces Apoptosis of Leishmania major Promastigotes in Vitro

Area of Science:

• Parasitology
• Pharmacology
• Drug Discovery

Background:

• Current treatments for cutaneous leishmaniasis, primarily pentavalent antimony compounds, exhibit unsatisfactory efficacy.
• Tamoxifen, an established estrogen receptor antagonist used in breast cancer therapy, possesses potential antileishmanial properties.

Purpose of the Study:

• To evaluate the in vitro antileishmanial activity of tamoxifen against promastigotes and amastigotes of the Leishmania major Iranian strain.
• To determine the half maximal inhibitory concentration (IC50) and assess the apoptotic effects of tamoxifen on Leishmania parasites.

Main Methods:

• In vitro exposure of Leishmania major promastigotes and amastigotes to varying concentrations and time points of tamoxifen.
• Quantification of parasite viability using the MTT assay and IC50 calculation with Graph Pad Prism software.
• Assessment of tamoxifen-induced apoptosis in promastigotes via flow cytometry analysis.

Main Results:

• Tamoxifen exhibited a half maximal inhibitory concentration (IC50) of 2.6 μg/ml against Leishmania major promastigotes after 24 hours of exposure.
• Flow cytometry revealed that tamoxifen significantly induced early and late apoptosis in Leishmania promastigotes, increasing from 2.0% in controls to 59.7% at 50 µg/L after 48 hours.
• Demonstrated in vitro efficacy suggests a potential therapeutic role for tamoxifen in leishmaniasis treatment.

Conclusions:

• Tamoxifen displays significant in vitro antileishmanial activity against Leishmania major, characterized by growth inhibition and apoptosis induction.
• The findings support the investigation of tamoxifen as a potential therapeutic agent for leishmaniasis.
• Further in vivo studies in animal models are warranted to confirm the efficacy and safety of tamoxifen for leishmaniasis treatment.