Inhibition by costunolide of phorbol ester-induced transcriptional activation of inducible nitric oxide synthase gene in a human monocyte cell line THP-1.

Costunolide, the predominant sesquiterpene lactone in Saussureae radix, has been reported to exhibit potent chemopreventive effects on carcinogenesis. Effects of costunolide on cellular activation induced by a tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) were investigated using a reporter gene assay which was designed to reflect the promoter activity of the inducible nitric oxide synthase (iNOS) gene in a human monocyte cell line THP-1. iNOS promoter-dependent reporter gene activity was significantly increased by TPA, and the TPA-induced increase of the reporter gene activity was efficiently reduced by costunolide, with an IC50 of approximately 2 microM. The addition of sulfhydryl (SH) compounds effectively abrogated the inhibitory effects of costunolide, suggesting the involvement of its reactivity with SH groups of target proteins and/or thiol-depleting property. The present findings may further explain the cancer-preventive property of costunolide.