title: Quercetin prevents liver carcinogenesis by inducing cell cycle arrest, decreasing cell proliferation and enhancing apoptosis.
abstract: METHODS
  Quercetin is the most abundant flavonoid in human diet. It has special interest as it holds anticancerous properties. This study aims to clarify the mechanisms involved in quercetin effects during the occurrence of preneoplastic lesions in rat liver.
  
  
  RESULTS
  Adult male Wistar rats were subjected to a two-phase model of hepatocarcinogenesis (initiated-promoted group). Initiated-promoted animals also received quercetin 10 and 20 mg/kg body weight (IPQ10 and IPQ20 groups, respectively). Antioxidant defenses were modified by quercetin administration at both doses. However, only IPQ20 group showed a reduction in number and volume of preneoplastic lesions. This group showed increased apoptosis and a reduction in the proliferative index. In addition, IPQ20 group displayed a reduction of cell percentages in G₁ and S phases, accumulation in G₂, and decrease in M phase, with reduced expression of cyclin D1, cyclin A, cyclin B, and cyclin-dependent kinase 1. Interestingly, peroxisome proliferator activated receptor-α levels were reduced in IPQ20 group.
  
  
  CONCLUSIONS
  The outcomes of this study represent a significant contribution to the current understanding on the preventive mechanisms of quercetin during the early stages of liver cancer development, demonstrating that in addition to its known proapoptotic characteristics, the flavonoid modulates the expression of critical cell cycle regulators and peroxisome proliferator activated receptor-α activity.
authors.affiliation: Instituto de Fisiología Experimental (IFISE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Rosario, Argentina.
authors.forename: María Laura
authors.initials: ML
authors.lastname: Casella
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Parody
authors.forename: María Paula
authors.initials: MP
authors.lastname: Ceballos
authors.forename: Ariel Darío
authors.initials: AD
authors.lastname: Quiroga
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Ronco
authors.forename: Daniel Eleazar
authors.initials: DE
authors.lastname: Francés
authors.forename: Juan Alberto
authors.initials: JA
authors.lastname: Monti
authors.forename: Gerardo Bruno
authors.initials: GB
authors.lastname: Pisani
authors.forename: Cristina Ester
authors.initials: CE
authors.lastname: Carnovale
authors.forename: María Cristina
authors.initials: MC
authors.lastname: Carrillo
authors.forename: María
authors.initials: M
authors.lastname: de Luján Alvarez
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D063646:Carcinogenesis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000517:prevention & control*; D008297:Male; D047493:PPAR alpha / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D047493:PPAR alpha; D019938:Cyclin D1; D011794:Quercetin; D016203:CDC2 Protein Kinase
keywords: Apoptosis; Preneoplastic liver; Proliferation; Quercetin