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-alpha (PKC-alpha), in concert with a time-dependent activation of key death-related signals: c-jun amino-terminal kinase (JNK) and PKC-delta. 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.
Granado-Serrano
Ana Belén
AB
Department of Metabolism and Nutrition, Instituto del Frío, Consejo Superior de Investigaciones Científicas (CSIC), José Antonio Novais 10, Ciudad Universitaria, Madrid, Spain.
Angeles Martín
María
M
Bravo
Laura
L
Goya
Luis
L
Ramos
Sonia
S
D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D011794:Quercetin / Q000627:therapeutic use*
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D011794:Quercetin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt