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.
Shimizu
Kazuo
K
Department of Life Science, Graduate School of Science and Technology, Kobe University, Kobe, Japan.
Das
Swadesh K
SK
Hashimoto
Takashi
T
Sowa
Yoshihiro
Y
Yoshida
Tatsushi
T
Sakai
Toshiyuki
T
Matsuura
Yukinaga
Y
Kanazawa
Kazuki
K
D015152:Blotting, Northern; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D056741:Cyclin D; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects*; D045325:HCT116 Cells; D006801:Humans; D047468:Immunoprecipitation; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D010666:Phenylpropionates / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011429:Propolis / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects*; D016160:Retinoblastoma Protein / Q000378:metabolism
D056741:Cyclin D; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019384:Nucleic Acid Synthesis Inhibitors; D010666:Phenylpropionates; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; C102259:artepillin C; D011429:Propolis; D051358:Cyclin-Dependent Kinase 4