Time-course regulation of quercetin on cell survival/ proliferation pathways in human hepatoma cells

Quercetin, a dietary flavonoid, has been shown to possess anticarcinogenic properties, but the precise molecular mechanisms of action are not thoroughly elucidated. This study was aimed at investigating the time-course regulation effect of quercetin on survival/proliferation pathways in a human hepatoma cell line (HepG2). Quercetin induced a significant time-dependent inactivation of the major survival signaling proteins, i. e., phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B (AKT), extracellular regulated kinase (ERK), protein kinase C-α (PKC-α), in concert with a time-dependent activation of key death-related signals: c-jun amino-terminal kinase (JNK) and PKC-δ. These data suggest that quercetin exerts a tight regulation of survival/proliferation pathways that requires the integration of different signals and persists over time, being the balance of these regulatory signals what determines the fate of HepG2 cells. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.This work was sup-ported by the grants AGL2004-302 from the Spanish Ministry of Science and Technology (CICYT), and 200570M050from the Comunidad de Madrid (CAM). A. B. G.–S. is a pre-doctoral fellow of the Spanish Ministry of Science and Edu-cation and S. R. has a Ramón y Cajal contract from theSpanish Ministry of Science and Technology.Peer reviewe