MURRAY Ana paula
congresos y reuniones científicas
Cativic acid-caffeic acid hybrid triggers apoptosis and inhibits proliferation of human neuroblastoma cells.
Mar del Plata
Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental; 2016
Institución organizadora:
Sociedad Argentina de Farmacología Experimental
A new approach in the field of drug discovery, including anticancer drugs, is the design and development of hybrids from natural products. Specifically, the search of anticancer agents that can induce apoptosis and the investigation of the signaling pathways involved in their effect constitute an emerging field of interest.The aim of this study was to evaluate the effect on cell growth and induction of apoptosis of a semisynthetic hybrid of 17-hydroxicativic acid and caffeic acid (1) on human neuroblastoma IMR-32 cells. In addition, we investigated the involvement of MAPK signaling pathways in the biological effect of 1.Hybrid 1 showed to inhibit cell growth with an IC50 value of 18.0 ± 1.3 μM (p < 0.05) and increased (p < 0.05) caspase-3 activity significantly in 1-treated cells. Additionally, BrDU positive cells diminished after exposure to 1 (10 μM) compared to control condition (36.6 ± 0.7% and 58.1 ± 0.9% respectively, p < 0.001). For further characterizing the biological effect of 1, we analyzed cell cycle distribution by flow cytometry. Cell population in S phase significantly increased after exposure to 1 (10 μM) with a reciprocal decrease in the G2/M phase compared to the control group (p < 0.001).We next investigated the state of MAPK, ERK1/2 and JNK. Levels of ERK1/2 phosphorylation were increased in IMR-32 cells exposed to 1(10 - 25 μM) for 12 and 24 h. This was accompanied by ERK1/2 and c-Jun nuclear translocation. For determining, the role of ERK1/2 and JNK in the bioactivity of 1we used pharmacological manipulation. Pretreatment with ERK inhibitor, U0126, and JNK inhibitor, SP600125, reduced cell viability compared with conditions treated with 1 alone (p < 0.001). In conclusion, hybrid 1 is able to trigger antiproliferative signals and apoptosis in IMR-32 cells and trough the inhibition of MAPK activity its biological effect could be enhanced.