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.[1]References
- Artepillin C in Brazilian propolis induces G(0)/G(1) arrest via stimulation of Cip1/p21 expression in human colon cancer cells. Shimizu, K., Das, S.K., Hashimoto, T., Sowa, Y., Yoshida, T., Sakai, T., Matsuura, Y., Kanazawa, K. Mol. Carcinog. (2005) [Pubmed]
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