Effect of deguelin on UVB-induced skin carcinogenesis

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

Research output: Contribution to journalArticle

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
StatePublished - Jun 2005
Externally publishedYes

Fingerprint

Carcinogenesis
Skin
AMP-Activated Protein Kinases
Skin Neoplasms
NADH Dehydrogenase
Neoplasms
Transcription Factor AP-1
Chemoprevention
Arachidonic Acid
Signal Transduction
Down-Regulation
Adenosine Triphosphate
Phosphorylation
deguelin
Messenger RNA
DNA

Keywords

  • 5′ AMP-activated kinase (AMPK)
  • Chemoprevention
  • Deguelin
  • Nonmelanoma skin cancer (NMSC)
  • Ultraviolet B radiation (UVB)

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Microbiology (medical)

Cite this

Gills, J., Kosmeder, J., Moon, R. C., Lantvit, D. D., & Pezzuto, J. M. (2005). Effect of deguelin on UVB-induced skin carcinogenesis. Journal of Chemotherapy, 17(3), 297-301.

Effect of deguelin on UVB-induced skin carcinogenesis. / Gills, Joell; Kosmeder, J.; Moon, R. C.; Lantvit, D. D.; Pezzuto, J. M.

In: Journal of Chemotherapy, Vol. 17, No. 3, 06.2005, p. 297-301.

Research output: Contribution to journalArticle

Gills, J, Kosmeder, J, Moon, RC, Lantvit, DD & Pezzuto, JM 2005, 'Effect of deguelin on UVB-induced skin carcinogenesis', Journal of Chemotherapy, vol. 17, no. 3, pp. 297-301.
Gills J, Kosmeder J, Moon RC, Lantvit DD, Pezzuto JM. Effect of deguelin on UVB-induced skin carcinogenesis. Journal of Chemotherapy. 2005 Jun;17(3):297-301.
Gills, Joell ; Kosmeder, J. ; Moon, R. C. ; Lantvit, D. D. ; Pezzuto, J. M. / Effect of deguelin on UVB-induced skin carcinogenesis. In: Journal of Chemotherapy. 2005 ; Vol. 17, No. 3. pp. 297-301.
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