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

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. © 2005 Wiley‐Liss, Inc.