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Quercetin prevents liver carcinogenesis by inducing cell cycle arrest, decreasing cell proliferation and enhancing apoptosis
Author(s) -
Casella María Laura,
Parody Juan Pablo,
Ceballos María Paula,
Quiroga Ariel Darío,
Ronco María Teresa,
Francés Daniel Eleazar,
Monti Juan Alberto,
Pisani Gerardo Bruno,
Carnovale Cristina Ester,
Carrillo María Cristina,
Luján Alvarez María
Publication year - 2014
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201300362
Subject(s) - quercetin , apoptosis , cell cycle , cyclin d1 , cell growth , carcinogenesis , cyclin , flavonoid , cell cycle checkpoint , pharmacology , cancer research , endocrinology , biology , medicine , chemistry , antioxidant , cancer , biochemistry
Scope 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. Methods and results Adult male W istar 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 ( IPQ 10 and IPQ 20 groups, respectively). Antioxidant defenses were modified by quercetin administration at both doses. However, only IPQ 20 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, IPQ 20 group displayed a reduction of cell percentages in G 1 and S phases, accumulation in G 2 , and decrease in M phase, with reduced expression of cyclin D 1, cyclin A , cyclin B , and cyclin‐dependent kinase 1. Interestingly, peroxisome proliferator activated receptor‐α levels were reduced in IPQ 20 group. Conclusion 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.