| First Author | Dai Y | Year | 2009 |
| Journal | Cancer Res | Volume | 69 |
| Issue | 11 | Pages | 4776-83 |
| PubMed ID | 19458067 | Mgi Jnum | J:149441 |
| Mgi Id | MGI:3848547 | Doi | 10.1158/0008-5472.CAN-08-4754 |
| Citation | Dai Y, et al. (2009) Peroxisome proliferator-activated receptor-gamma contributes to the inhibitory effects of Embelin on colon carcinogenesis. Cancer Res 69(11):4776-83 |
| abstractText | Down-regulation of XIAP (X-linked inhibitor of apoptosis protein) sensitizes colon cancer cells to the anticancer effect of peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands in mice. The aims of this study were to evaluate the effect of embelin (2,5-dihydroxy-3-undecyl-1,4-benzoquinone), an antagonist of XIAP, on colon cancer, with a particular focus on whether PPARgamma is required for embelin to exert its effect. A dominant-negative PPARgamma was used to antagonize endogenous PPARgamma in HCT116 cells. Cells were treated with or without embelin. Cell proliferation, apoptosis, and nuclear factor-kappaB (NF-kappaB) activity were measured. For in vivo studies, 1,2-dimethylhydrazine dihydrochloride (DMH) was s.c. injected to induce colon cancer in PPARgamma(+/+) and PPARgamma(+/-) mice. Mice were fed embelin daily for 10 days before DMH injection, and continued for 30 more weeks. Embelin inhibited proliferation and induced apoptosis in HCT116 cells with marked up-regulation of PPARgamma. In addition, embelin significantly inhibited the expressions of survivin, cyclin D1, and c-Myc. These effects were partially dependent on PPARgamma. PPARgamma(+/-) mice were more susceptible to DMH-induced colon carcinogenesis than PPARgamma(+/+) mice, and embelin significantly reduced the incidence of colon cancer in PPARgamma(+/+) mice but not in PPARgamma(+/-) mice. Embelin inhibited NF-kappaB activity in PPARgamma(+/+) mice but marginally so in PPARgamma(+/-) mice. Thus, reduced expression of PPARgamma significantly sensitizes colonic tissues to the carcinogenic effect of DMH. Embelin inhibits chemical carcinogen-induced colon carcinogenesis, but this effect is partially dependent on the presence of functional PPARgamma, indicating that PPARgamma is a necessary signaling pathway involved in the antitumor activity of normal organisms. |
