ADVANCES IN THE STUDY OF ANTHRACYCLINES EFFECT ON TRYPANOSOMA CRUZI

MD, RUIZ; L. FRACCAROLI,; BALCAZAR, D; VANRELL. C; L. LAROCCA; P. ROMANO; CARRILLO C

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2019; 2019

Trypanosoma cruzi (T. cruzi) is theetiological agent of Chagas disease. As current therapies arelimited in efficacy, there is a need to identify new specifictrypanocidal compounds. Our previous work showed thatanthracyclines (antitumor agents) decreased survival andproliferation of T. cruzi epimastigotes and interfered with itsputrescine uptake. The aim of this work was to deepen the studyabout anthracyclines effect on polyamine metabolism inepimastigotes and to analyze their effect on different T. cruzi lifecycle stages. Daunorubicin (Dnr) and Doxorubicin (Dxr) were theanthracyclines selected to evaluate their effect on T. cruzi (strainY-GFP). We performed growth curves, and measured intracellularcontent of polyamines, by HPLC analysis, on epimastigotescultured in putrescine depleted medium for 1 to 15 days. Underthese conditions, intracellular putrescine diminished and T. cruziepimastigotes became significatively more sensitive to Dnr andDxr (IC50 of 0.1 μM for Dnr and 2 μM for Dxr), not depending onthe nutritional stress length. On the other hand, although Dxrand Dnr interfere with polyamine uptake, sub-IC50 doses ofthese did not change the intracellular concentration of putrescineduring 15 days of culture. Anthracyclines effect was tested in invitro metacyclogenesis, infectivity and amastigotes proliferationassays. Differentiation from epimastigotes to metacyclictrypomastigotes diminished by Dnr treatment (from 14.8 % incontrol condition to 8.9 % with Dnr). Dnr did not affect thenumber of infected H9C2 cells nor total number of these cells butreduced by half the number of amastigotes per cell. The findingspresented herein showed that Dnr and Dxr affect T. cruziepimastigotes survival and proliferation, metacyclogenesis andreplicative capacity of amastigotes. This effect could be related tothe decrease of polyamine uptake by anthracyclines and theirintracellular toxic effects.