interleukin-8 and deguelin

Deguelin, a naturally occurring rotenoid, is known to be an Akt inhibitor and to have an anti-tumor effect on several cancers.. This study was performed to elucidate the effect of deguelin on apoptotic pathways related to NF-κB signaling in colon cancer cells and on the anti-tumor effect in colon cancer xenograft mice.. We studied COLO 205 and HCT116 cells in the presence or absence of deguelin. NF-κB signaling was examined by real-time RT-PCR for interleukin (IL)-8, by Western blotting for IκB phosphorylation/degradation, and by the electrophoretic mobility shift assay. Cell death was determined by the MTT assay, and apoptosis by Annexin V-FITC staining and caspase-3 activity. We also assessed the expression of antiapoptotic and proapoptotic factors by use of RT-PCR. In colon cancer xenograft mice, we evaluated the effect of deguelin on inoculated tumor growth, and apoptotic index was measured by the in vivo TUNEL assay.. Deguelin significantly inhibited IL-8 gene expression, IκB phosphorylation/degradation, and DNA binding activity of NF-κB in colon cancer cells. Deguelin induced cell death and apoptosis in colon cancer cells in a dose and time-dependent manner. Deguelin down-regulated expression of NF-κB-mediated antiapoptotic factors such as cFLIP, Bcl-2, and Bcl-X(L). In the colon cancer xenograft model, the volume of the tumor treated with deguelin was significantly lower than that of the control, and the apoptotic index for deguelin-treated mice was much higher.. Deguelin might be a potential therapeutic agent for treatment of colorectal cancer.

Topics: Animals; Apoptosis; bcl-X Protein; Blotting, Western; CASP8 and FADD-Like Apoptosis Regulating Protein; Caspase 3; Cell Line, Tumor; Colonic Neoplasms; Down-Regulation; In Situ Nick-End Labeling; Interleukin-8; Mice; NF-kappa B; Proto-Oncogene Proteins c-bcl-2; Real-Time Polymerase Chain Reaction; Rotenone; Signal Transduction; Statistics, Nonparametric