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

Authors
Won-YK; Ong-CN; Shi-X; Shen-HM
Source
Carcinogenesis 2004 Aug; 25(8):1449-1458
NIOSHTIC No.
20025981
Abstract
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.
Keywords
Cancer; Skin-cancer; In-vivo-studies; In-vitro-studies; Models; Laboratory-animals; Animals; Animal-studies
Contact
Department of Community, Occupational, and Family Medicine, Faculty of Medicine, National University of Singapore, 16 Medical Drive, Singapore 117597, Republic of Singapore
CODEN
CRNGDP
Publication Date
20040801
Document Type
Journal Article
Email Address
cofshm@nus.edu.sg
Fiscal Year
2004
NTIS Accession No.
NTIS Price
Issue of Publication
8
ISSN
0143-3334
NIOSH Division
HELD
Source Name
Carcinogenesis
State
WV
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