Abstract
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 TNFα 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.
Original language | English (US) |
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Pages (from-to) | 297-301 |
Number of pages | 5 |
Journal | Journal of Chemotherapy |
Volume | 17 |
Issue number | 3 |
DOIs | |
State | Published - Jun 2005 |
Externally published | Yes |
Keywords
- 5′ AMP-activated kinase (AMPK)
- Chemoprevention
- Deguelin
- Nonmelanoma skin cancer (NMSC)
- Ultraviolet B radiation (UVB)
ASJC Scopus subject areas
- Oncology
- Pharmacology
- Pharmacology (medical)
- Infectious Diseases