5-epi-icetexane affects the proliferation of Trypanosoma cruzi by multiple molecular mechanisms.

A.M. SANCHEZ; J. ETCHEGOREN; T. SARTOR; C. TONN; M. NIETO; EE. GARCIA; MH. BURGOS; MT. TÉLLEZ-IÑON; MA. SOSA

Merlo, San Luis, Argentina

Congreso; XXII Annual Scientific Meeting. Cuyo Biology Society; 2004

SOCIEDAD BIOLOGIA DE CUYO

Trypanosoma cruzi is the etiological agent of chagas’ disease. In cultures, these parasites cycle between different forms of the flagellate epimastigote, and scarcely differentiate to the infective trypomastigote. Since decades, several natural compounds have been used as trypanocidal agents at the acute phase of the disease. Quinones have shown to be effective against the parasite, although their use is still restricted because a cytotoxic effect on the host cells. We previously demonstrated that an hydroxylated quinone, 5-epi-icetexane (ICTX), purified from Salvia gilliesi, exhibited an antiproliferative effect on cultured T.cruzi epimastigotes, even at very low concentrations. The present work was addressed to understand the mechanism of that antiproliferative effect. The growth of the parasites was synchronized at G1 phase by treatment with hydroxyurea (HU) for 24 hr, and ICTX was added at different time points after removal of HU. We observed that ICTX is able to arrest the cell cycle of the parasites at the time corresponding to S phase, and at lesser extent when added at G2 phase. We also evaluated if expression of particular proteins was affected by the drug, and observed no differences in the protein patterns. However, proteins in the range of 30-70 kDa exhibited higher phosphorylation in serine and tyrosine residues than those in the controls. Among these proteins, p53 appeared as a target for the action of ICTX, as shown by a Western blot analysis. We conclude that ICTX exerts an antiproliferative effect on T.cruzi by inducing phosphorylation of certain proteins that regulate the cell cycle of the parasites.