| First Author | Gills JJ | Year | 2005 |
| Journal | J Chemother | Volume | 17 |
| Issue | 3 | Pages | 297-301 |
| PubMed ID | 16041863 | Mgi Jnum | J:101510 |
| Mgi Id | MGI:3604182 | Doi | 10.1179/joc.2005.17.3.297 |
| Citation | Gills JJ, et al. (2005) Effect of deguelin on UVB-induced skin carcinogenesis. J Chemother 17(3):297-301 |
| abstractText | Nonmelanoma skin cancer afflicts more than one million people in the U.S. annually, highlighting the need for more effective preventive regimens. We have investigated the ability of deguelin, a plant-derived rotenoid with cancer chemopreventive activity, to inhibit UVB-induced skin carcinogenesis with the SKh-1 mouse model. Topically-applied deguelin significantly inhibited the multiplicity of UVB-induced skin tumors, indicating potential as a human skin cancer chemopreventive agent. Mechanistic studies to determine the potential of deguelin to block a number of established UVB-induced molecular events yielded negative results [including UVB-induced AP-1 DNA binding, c-fos and TNFalpha mRNA induction, arachidonic acid release and UVB-induced phosphorylation of mTOR (Ser2448), akt (Ser473) and erk (Thr202/Tyr204)]. These results are of interest as they contradict a major hypothesis for the mode of action of deguelin, i.e., a general down regulation of signal transduction based on inhibition of NADH dehydrogenase and depletion of ATP levels. In the current work, however, deguelin was found to activate 5' AMP-activated kinase (AMPK), a protein that acts as a cellular energy sensor. This is the first report of a chemopreventive agent having this effect and suggests a possible role for AMPK in cancer chemoprevention. |
