Effects of low dose quercetin: cancer cell-specific inhibition of cell cycle progression

J Cell Biochem. 2009 Jan 1;106(1):73-82. doi: 10.1002/jcb.21977.


Quercetin is a flavonoid present in many vegetables, fruits, and beverages. Due to its anti-oxidant, anti-tumor, and anti-inflammatory activity, quercetin has been studied extensively as a chemoprevention agent in several cancer models. Since most of these studies used higher doses of quercetin than clinically achievable, we focused on the effectiveness of physiologically relevant doses of quercetin. A low dose of quercetin exerted cancer cell-specific inhibition of proliferation and this inhibition resulted from cell cycle arrest at the G(1) phase. Quercetin induced p21 CDK inhibitor with a concomitant decrease of phosphorylation of pRb, which inhibits the G(1)/S cell cycle progression by trapping E2F1. A low dose of quercetin induced mild DNA damage and Chk2 activation, which is the main regulator of p21 expression by quercetin. In addition, quercetin down-regulated the cyclin B1 and CDK1, essential components of G(2)/M cell cycle progression. Inhibition of the recruitment of key transcription factor NF-Y to cyclin B1 gene promoter by quercetin led to transcriptional inhibition. This study proved that the chemo-preventive efficacy of a physiologically relevant dose of quercetin can be achievable through the inhibition of cell cycle progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anticarcinogenic Agents / pharmacology*
  • Antioxidants / pharmacology*
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism
  • Cell Cycle / drug effects*
  • Cell Proliferation / drug effects
  • Checkpoint Kinase 2
  • Cyclin B / genetics
  • Cyclin B / metabolism
  • Cyclin B1
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • DNA Damage
  • Dose-Response Relationship, Drug
  • Humans
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Quercetin / pharmacology*
  • Transcription, Genetic
  • Tumor Cells, Cultured


  • Anticarcinogenic Agents
  • Antioxidants
  • CCNB1 protein, human
  • Cyclin B
  • Cyclin B1
  • Cyclin-Dependent Kinase Inhibitor p21
  • Quercetin
  • Checkpoint Kinase 2
  • CHEK2 protein, human
  • Protein Serine-Threonine Kinases
  • CDC2 Protein Kinase