Artepillin C in Brazilian propolis induces G(0)/G(1) arrest via stimulation of Cip1/p21 expression in human colon cancer cells

Mol Carcinog. 2005 Dec;44(4):293-9. doi: 10.1002/mc.20148.

Abstract

Potential chemopreventive agents exist in foods. Artepillin C in Brazilian propolis was investigated for its effects on colon carcinogenesis. We had found that artepillin C was a bioavailable antioxidant, which could be incorporated into intestinal Caco-2 and hepatic HepG2 cells without any conjugation and inhibited the oxidation of intracellular DNA. Artepillin C was then added to human colon cancer WiDr cells. It dose-dependently inhibited cell growth, inducing G(0)/G(1) arrest. The events involved a decrease in the kinase activity of a complex of cyclin D/cyclin-dependent kinase 4 and in the levels of retinoblastoma protein phosphorylated at Ser 780 and 807/811. The inhibitors of the complex, Cip1/p21 and Kip1/p27, increased at the protein level. On the other hand, Northern blotting showed that artepillin C did not affect the expression of Kip1/p27 mRNA. According to the experiments using isogenic human colorectal carcinoma cell lines, artepillin C failed to induce G(0)/G(1) arrest in the Cip1/p21-deleted HCT116 cells, but not in the wild-type HCT116 cells. Artepillin C appears to prevent colon cancer through the induction of cell-cycle arrest by stimulating the expression of Cip1/p21 and to be a useful chemopreventing factor in colon carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Cyclin D
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Cyclins / metabolism
  • Flow Cytometry
  • G1 Phase / drug effects*
  • HCT116 Cells
  • Humans
  • Immunoprecipitation
  • Nucleic Acid Synthesis Inhibitors / pharmacology*
  • Phenylpropionates / pharmacology*
  • Phosphorylation / drug effects
  • Propolis / chemistry*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Resting Phase, Cell Cycle / drug effects*
  • Retinoblastoma Protein / metabolism

Substances

  • Cyclin D
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Nucleic Acid Synthesis Inhibitors
  • Phenylpropionates
  • RNA, Messenger
  • Retinoblastoma Protein
  • Cyclin-Dependent Kinase Inhibitor p27
  • artepillin C
  • Propolis
  • Cyclin-Dependent Kinase 4