Deguelin, an Akt Inhibitor, Down-Regulates NF-kappa B Signaling and Induces Apoptosis in Colon Cancer Cells and Inhibits Tumor Growth in Mice
- Authors
- Kang, Hyoun Woo; Kim, Jung Mogg; Cha, Mi Yeon; Jung, Hyun Chae; Song, In Sung; Kim, Joo Sung
- Issue Date
- Nov-2012
- Publisher
- SPRINGER
- Keywords
- Deguelin; Colon cancer; NF-kappa B; Apoptosis
- Citation
- DIGESTIVE DISEASES AND SCIENCES, v.57, no.11, pp.2873 - 2882
- Indexed
- SCIE
SCOPUS
- Journal Title
- DIGESTIVE DISEASES AND SCIENCES
- Volume
- 57
- Number
- 11
- Start Page
- 2873
- End Page
- 2882
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/164295
- DOI
- 10.1007/s10620-012-2237-x
- ISSN
- 0163-2116
- Abstract
- 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-kappa B 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-kappa B signaling was examined by real-time RT-PCR for interleukin (IL)-8, by Western blotting for I kappa B 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, I kappa B phosphorylation/degradation, and DNA binding activity of NF-kappa B 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-kappa B-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.
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