Possible effect of 5-epi-icetexane on early G2-phase of the Trypanosoma cruzi cell cycle

ESTEBAN LOZANO; TIRSO SARTOR; CARLOS TONN; MATÍAS NIETO; EDUARDO GARCÍA; MIGUEL A. SOSA

Potrero de los Funes (San Luis)

Congreso; XXIV Reunión Científica Anual Sociedad de Biología de Cuyo. IV Reunión Anual de la Sociedad Argentina de Microscopía; 2006

Sociedad de Biología de Cuyo

Possible effect of 5-epi-icetexane on early G2-phase of the Trypanosoma cruzi cell cycle.   Lozano E, Sartor T, Tonn C*, Nieto M*, García EE*, and  Sosa MA. IHEM-CONICET- UNCuyo Mendoza. *INTEQUI-CONICET?UNSL, 5700 San Luis. Trypanosoma cruzi is the etiological agent of chagas? disease. In cultures, these parasites cycle between the flagellate epimastigote form, and scarcely differentiate to the infective trypomastigote. Quinones derivatives have shown to be effective against the parasite, although their use is still restricted because a cytotoxic effect on the host cells. A novel 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 evaluate if the drug affects selectively certain phase of the parasite cell cycle.  The growth of the parasites (Dm28c strain) was synchronized at G1 phase by treatment with hydroxyurea (HU)  for 24 hr, and cytostatic concentrations of ICTX were added at different time points after removal of HU. We observed that ICTX is able to arrest  selectively the cell cycle between 12 and 14 hours after  removal  the HU.   No major effect was observed at earlier time point, corresponding to the S phase of the cell cycle.   We concluded that  ICTX affects early G2 phase of the cell cycle,  probably by knocking down  expression  of important regulating proteins.   Ultrastructural studies will confirm if ICTX affects somehow the chromatin condensation,  impeding  cell division.