INVESTIGADORES
CARRILLO carolina
congresos y reuniones científicas
Título:
Advances in the study of anthracyclines effect on Trypanosoma cruzi
Autor/es:
RUIZ MD; FRACCAROLI L; BALCAZAR DE; VANRELL MC; LAROCCA L; ROMANO PS; CARRILLO C
Lugar:
Mar del Plata
Reunión:
Congreso; Reunión Anual de Sociedades de Biociencias; 2019
Institución organizadora:
SAP, SAB, SAFE, SAIC
Resumen:
Trypanosoma cruzi (T. cruzi) is the etiological agent of Chagas disease. As current therapies arelimited in efficacy, there is a need to identify new specific trypanocidal compounds.Our previous work showed that anthracyclines (antitumor agents) decreased survival andproliferation of T. cruzi epimastigotes and interfered with its putrescine uptake. The aim of thiswork was to deepen the study about anthracyclines effect on polyamine metabolism inepimastigotes and to analyze their effect on different T. cruzi life cycle stages.Daunorubicin (Dnr) and Doxorubicin (Dxr) were the anthracyclines selected to evaluate their effecton T. cruzi, strains Y-GFP and Y-TcPAT12-GFP (that overexpress TcPAT12, a polyamine permease).We performed growth curves, and measured intracellular content of polyamines, by HPLC analysis,on epimastigotes cultured in putrescine depleted medium for 1 to 15 days. Under theseconditions, intracellular putrescine diminished and T. cruzi epimastigotes became significativelymore sensitive to Dnr and Dxr (IC50 of 0.1μM for Dnr and 2μM for Dxr), not depending on thenutritional stress length. On the other hand, although Dxr and Dnr interfere with polyamineuptake, sub-IC50 doses of them didn?t change concentrations of intracellular putrescine along 15days of culture.Anthracyclines effect was tested in in vitro metacyclogenesis, infectivity and amastigotesproliferation assays. Differentiation from epimastigotes to metacyclic trypomastigotes diminishedby Dnr treatment (from 14,8% in control condition to 8,9% with Dnr). Dnr didn?t affect the numberof infected H9C2 cells nor total number of these cells, but reduced to half the number ofamastigotes per cell.The findings presented herein showed that Dnr and Dxr affect T. cruzi epimastigotes survival andproliferation, metacyclogenesis and replicative capacity of amastigotes. This effect could berelated to the decrease of polyamine uptake by anthracyclines and their intracellular toxic effects.