The chemopreventive property of parthenolide, A Sesquiterpene lactone

Abstract

Parthenolide (PN) is the principal sesquiterpene lactone of feverfew (Tanacetum parthanium) with known anti-inflammatory activity. The main objective of this study is to systematically evaluate the anti-cancer property of parthenolide using a combination of in vivo and in vitro approaches. We first tested the anti-cancer effect of PN in UVB-induced skin cancer model. SKH-1 hairless 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 to the UVB-only group. We next investigated the molecular mechanism(s) involved in its anti-cancer effects using cultured JB6 murine epidermal cells. Non-cytotoxic concentrations of PN selectively promote PKCI' but suppress PKCI?. In addition, PN pretreatment also inhibited c-Jun-N-terminal kinase (JNK) and p38 kinase activation, leading to suppression of the pro-survival AP-1 transcription factor. More importantly, we found that selective regulation of PKC, impaired AP-1, JNK and p38 signaling lead to the sensitization of JB6 cells to UVB-induced apoptosis.