Quercetin prevents liver carcinogenesis by inducing cell cycle arrest, decreasing cell proliferation and enhancing apoptosis
Article first published online: 1 OCT 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 58, Issue 2, pages 289–300, February 2014
How to Cite
Casella, M. L., Parody, J. P., Ceballos, M. P., Quiroga, A. D., Ronco, M. T., Francés, D. E., Monti, J. A., Pisani, G. B., Carnovale, C. E., Carrillo, M. C. and de Luján Alvarez, M. (2014), Quercetin prevents liver carcinogenesis by inducing cell cycle arrest, decreasing cell proliferation and enhancing apoptosis. Mol. Nutr. Food Res., 58: 289–300. doi: 10.1002/mnfr.201300362
- Issue published online: 3 FEB 2014
- Article first published online: 1 OCT 2013
- Manuscript Accepted: 9 JUL 2013
- Manuscript Revised: 4 JUL 2013
- Manuscript Received: 17 MAY 2013
- Consejo Nacional de Investigaciones Científicas y Técnicas
- Fundación Florencio Fiorini
- Preneoplastic liver;
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 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.
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.