Effect of promethazine and hydroxyzine, two inhibitors of Tumor Controlled Translational Protein (TCTP), on the growth of in vitro culture of Trypanosoma brucei gambiense and Trypanosoma congolense

Résumé fourni par la source

TCTP, an ubiquitous protein excreted by trypanosomes when cultured in vitro, has also been identified in the intestine of the tsetse fly and in the blood of infected mammalian hosts. Recombinant TCTP was able to modulate the growth of tsetse fly intestinal bacteria and mice immunization with this recombinant protein its survival after challenge with the parasite. TCTP is involved in a number of biological processes, including cancer expansion; TCTP inhibitors have been shown to reduce or even suppress the multiplication of tumor cells. In this study, we have tested the efficiency of two TCTP inhibitors, promethazine and hydroxyzine, on the growth and survival of Trypanosoma brucei gambiense (Tbg) and T. congolense (Tc) pathogenic for humans and animals, respectively. The effectiveness of the inhibitors was assessed by measuring the ED50 (Effective Dose), i.e. the concentration of inhibitor required to reduce, for a given incubation time, the growth of the tested trypanosome species by 50%. Both inhibitors slowed down the multiplication of parasites but differed in their efficiencies, promethazine being more effective than hydroxyzine in reducing the growth of both Tc and Tbg. For example, regarding Tc, the ED50 was reached after a 24 h incubation in the culture medium supplemented with promethazine at a 5 μM concentration, whereas a concentration of 40 μM of hydroxyzine to obtain a similar result. Finally, Tbg was shown to be much more sensitive to both inhibitors than Tc. The results, which were obtained in vitro, show that TCTP is involved in the development/multiplication of both trypanosome species, one of which, Tbg, being pathogenic for humans. The next step will be to verify the possible effect of treatment with TCTP inhibitors on infection of mice with trypanosomes.

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