Inhibitory effect of quercetin on the intracellular signaling and cell cycle in insulin-stimulated cell line.

SARAGUSTI ALEJANDRA; ORTEGA GABRIELA; CABRERA JOSÉ LUIS; CHIABRANDO GUSTAVO

Iguazu

Congreso; XL Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB). (2004).; 2004

Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB).

INHIBITORY EFFECT OF QUERCETIN ON THE INTRACELLULAR SIGNALING AND CELL CYCLE IN INSULIN-STIMULATED CELL LINE Saragusti, A¹; Ortega G²; Cabrera JL² and Chiabrando G¹. ¹Departamento de Bioquímica Clinica-CIBICI (CONICET) and ²Departamento de Farmacia-Facultad de Ciencias Químicas.UNC. Quercetin is the major flavonoid present in human diet which contain anti-inflammatory and anti-carcinogenic properties by inhibiting several intracellular signaling pathways. Although the main action of Insulin is to control the glucose level, also can regulate the cellular growth and differentiation mediated by its receptor (IR). This receptor is a tyrosine kinase receptor that down-stream activate signaling pathways such as PI3K/Akt and Ras/Raf. The Insulin Resistance Syndrome (IRS) is characterized by the inability of glucose control and plasma hyperinsulin mainly developed during Type II Diabetes and stress, which has been associated with atherosclerosis and cancer development. In the present work we evaluate the inhibitory effect of Quercetin on intracellular signaling and cell cycle in insulin-stimulated CHOK1 cell line . By western blotting we measure phosphorylated ERK-1/2 (ERK-p) in the presence of Quercetin 100 mM (preincubated for 30 min) and diverse doses of Insulin (1.10 -4 to 1.0 U/ml) for several time of incubation (15 to 240 min.). We demonstrate that Quercetin increase the Insulin activity on ERK-p at short time of incubation (up to 90 min) but exert an inhibitory effect on ERK-p after 90 min of insulin incubation. In addition, by FACS analysis we demonstrate that Quercetin can inhibit the proliferation effect of insulin on CHOK1 cell line. In conclusion, in this work we demonstrate that Quercetin modify the insulin activity mainly on intracellular signaling and cellular proliferation.