The hedgehog (Hh) signaling pathway is an important regulator of embryonic development, tissue patterning, cellular proliferation and differentiation. However, aberrant activation of the pathway is associated with tumorigenesis. In this study, the Hh signal inhibitory activity of plant extracts was measured with a cell-based assay system that targets GLI1-mediated transcription. Activity guided analysis of MeOH extracts of christmas grass (Themeda arguens) led to the isolation of four inhibitory compounds: Aciculatin (1), 7-de-O-methylaciculatin (2), 8-C-D-boivinopyranosylapigenin (3) and aciculatinone (4). Compound 1 strongly inhibited Hh/GLI1-mediated transcriptional activity with an IC50 value of 1.8 ΓM, and disrupted the formation of the GLI1-DNA complex by EMSA. 1 and 3 were cytotoxic for human prostate (DU-145) and breast (MCF-7) cancer cells. These compounds may serve as new tools for the molecular dissection of Hh pathway activation.
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