Cytotoxic activity of bioactive compounds isolated from Flourensia oolepis S. F. Blake

JORAY M.; TRUCCO L.; GONZÁLEZ M.; BOCCO J.; CARPINELLA C.

Encuentro; 3° Reunión Internacional de Ciencias Farmacéuticas RICIFA.; 2014

Previously, five antibacterial flavonoids identified as 2´,4´-dihydroxychalcone (1), isoliquiritigenin (2), pinocembrin (3), 7-hydroxyflavanone (4) and 7,4´-dihydroxy-3´-methoxyflavanone (5) were isolated by bio-guided fractionation from the ethanol extract of Flourensia oolepis S. F. Blake. This time, the cytotoxicity of these compounds against two leukemic cell lines and their respective multidrug resistant counterparts was evaluated. Compound 1 showed the strongest cytotoxic effect against CCRF-CEM and its MDR variant CEM/ADR5000 (IC50 = 1.6 and 2.4 g/ml, respectively). It also showed a moderate effect against K562 and the MDR line Lucena 1 (IC50 = 6.6 and 7.4 g/ml, respectively). A lack of cross resistance toward the MDR cells was evidenced in opposite to that found in treatments with the chemotherapeutic agent doxorubicin. In addition, 1 induced a dose and time dependent growth inhibition. 72 h exposure of CCRF-CEM to 1.25 g/mL and 2.5 g/mL resulted in 46% and 85% of growth inhibition while in K562 this last grade of inhibition was achieved at 10 g/mL. Analysis of DNA content by flow cytometry indicated that treatments of CCRF-CEM with 1 resulted in an accumulation of cells in G2/M phase. After 72 h of exposure, the percentage of cells in this phase was 47% compared to 11% in control cells. On the other hand, K562 cells showed a significant increase in the proportion of cells in S and G2/M phases. Annexin V staining showed that 1 induced CCRF-CEM and K562 apoptosis reaching 26 and 27%, respectively, after 72 h of treatment. As far as we know this is the first time that the anti-proliferative activity of 1 over these leukemic cell lines is reported. These results suggest that 1-induced suppression on cell growth would be possibly mediated by slowing down cellular progress through G2/M phase or even blocking cells in this phase accompanied by apoptosis on both leukemic lines.