Effect of deguelin on UVB-induced skin carcinogenesis

J. J. Gills, J. Kosmeder, R. C. Moon, D. D. Lantvit, J. M. Pezzuto

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)297-301
Number of pages5
JournalJournal of Chemotherapy
Volume17
Issue number3
DOIs
StatePublished - Jun 2005
Externally publishedYes

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

Fingerprint

Dive into the research topics of 'Effect of deguelin on UVB-induced skin carcinogenesis'. Together they form a unique fingerprint.

Cite this