Chemopreventive activity of parthenolide against UVB-induced skin cancer and its mechanisms

Carcinogenesis. 2004 Aug;25(8):1449-58. doi: 10.1093/carcin/bgh151. Epub 2004 Mar 19.


Parthenolide (PN) is a major sesquiterpene lactone of feverfew (Tanacetum parthanium) with known anti-inflammatory activity. However, the anticancer effects of PN have not been well studied. In the present investigation, we examined the cancer chemopreventive property of PN using a combination of in vivo and in vitro approaches. We first tested the anticancer effect of PN in UVB-induced skin cancer model. Mice fed with PN (1 mg/day) showed a delayed onset of papilloma incidence, a significant reduction in papilloma multiplicity (papilloma/mouse) and sizes when compared with the UVB-only group. To our surprise, neither PN nor the known cyclooxygenase (COX)-2 inhibitor celecoxib inhibit UVB-induced COX-2 expression and epidermal prostaglandin E2 (PGE2) production. We next investigated the molecular mechanism(s) involved in its anticancer effects using cultured JB6 murine epidermal cells. Non-cytotoxic concentrations of PN significantly inhibited UVB-induced activator protein-1 DNA binding and transcriptional activity. In addition, PN pre-treatment also inhibited c-Jun-N-terminal kinase (JNK) and p38 kinase activation. More importantly, we found that impaired AP-1, JNK and p38 signaling led to the sensitization of JB6 cells to UVB-induced apoptosis. Data from our study for the first time confirm the anticancer property of PN in an animal model, and provide evidence that the inhibitory effects on AP-1 and mitogen-activated protein kinases serve as one of the underlying mechanisms for the cancer chemopreventive property of PN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anticarcinogenic Agents / pharmacology*
  • Apoptosis
  • Blotting, Western
  • Celecoxib
  • Cell Death
  • Cyclooxygenase 2
  • DNA / metabolism
  • Dinoprostone / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Epidermal Cells
  • Female
  • Immunohistochemistry
  • Isoenzymes / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Signaling System
  • Mice
  • Mice, Hairless
  • Mitogen-Activated Protein Kinases / metabolism
  • Models, Chemical
  • Neoplasms, Radiation-Induced / prevention & control*
  • Papilloma / prevention & control
  • Phosphorylation
  • Prostaglandin-Endoperoxide Synthases
  • Protein Binding
  • Pyrazoles
  • Sesquiterpenes / pharmacology*
  • Skin Neoplasms / etiology
  • Skin Neoplasms / prevention & control*
  • Sulfonamides / pharmacology
  • Time Factors
  • Transcription Factor AP-1 / metabolism
  • Transcription, Genetic
  • Transcriptional Activation
  • Ultraviolet Rays*
  • p38 Mitogen-Activated Protein Kinases


  • Anti-Inflammatory Agents, Non-Steroidal
  • Anticarcinogenic Agents
  • Enzyme Inhibitors
  • Isoenzymes
  • Pyrazoles
  • Sesquiterpenes
  • Sulfonamides
  • Transcription Factor AP-1
  • parthenolide
  • DNA
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Celecoxib
  • Dinoprostone