Premium
Artepillin C in Brazilian propolis induces G 0 /G 1 arrest via stimulation of Cip1/p21 expression in human colon cancer cells
Author(s) -
Shimizu Kazuo,
Das Swadesh K.,
Hashimoto Takashi,
Sowa Yoshihiro,
Yoshida Tatsushi,
Sakai Toshiyuki,
Matsuura Yukinaga,
Kanazawa Kazuki
Publication year - 2005
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20148
Subject(s) - biology , carcinogenesis , colorectal cancer , kinase , g1 phase , cell cycle checkpoint , cancer research , cell cycle , microbiology and biotechnology , cancer , cell , biochemistry , genetics
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.