Chemopreventive Activity of Parthenolide Against UVB-Induced Skin Cancer and Its Mechanisms

Details

• Personal Author:
  Ong C-N ; Shen H-M ; Shi X ; Won Y-K
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Animals Laboratories Neoplasms Occupational Health Safety Skin Skin Diseases
• Keywords:
  Animal-studies Cancer In-vitro-studies In-vivo-studies Laboratory-animals Models Skin-cancer
• ISSN:
  0143-3334
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  25
• Issue:
  8
• NIOSHTIC Number:
  nn:20025981
• Citation:
  Carcinogenesis 2004 Aug; 25(8):1449-1458
• Contact Point Address:
  Yen-Kim Won, Department of Community, Occupational, and Family Medicine, Faculty of Medicine, National University of Singapore, 16 Medical Drive, Singapore 117597, Republic of Singapore
• Email:
  cofshm@nus.edu.sg
• Federal Fiscal Year:
  2004
• Peer Reviewed:
  True
• Source Full Name:
  Carcinogenesis
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4a75410c4c4256cc196e35c48deaedc23a55806914a72d049f545ea762b80e5deed5d65330773c9aaaa9d760b445676341f4f07115a917bcf0a49102df1138f4
• Download URL:
  https://stacks.cdc.gov/view/cdc/197132/cdc_197132_DS1.pdf
• File Type:
  [PDF - 1.94 MB ]