Sutherlanida extract inhibits Hedgehog signaling target genes

Sutherlandia frutescens (L) R. Br. (Sutherlandia) is a South African botanical that is traditionally used to treat a variety of health conditions, infections and diseases, including cancer. We hypothesized Sutherlandia might act through Gli/ Hedgehog (Hh)-signaling in prostate cancer cells and used RNA-Seq transcription profiling to profile gene expression in TRAMPC2 murine prostate cancer cells with or without Sutherlandia extracts. We found 50% of Hh-responsive genes can be repressed by Sutherlandia ethanol extract, including the canonical Hh-responsive genes Gli1 and Ptch1 as well as newly distinguished Hh-responsive genes Hsd11b1 and Penk. Using mouse prostate cancer TRAMPC2 cells, we treated TRAMPC2 cells with Hh ligand conditioned medium (Hh-CM), 8ug/ml or 80ug/ml Sutherlandia, co-treatment of Hh-CM with 8ug/ml or 80ug/ml Sutherlandia for 8 or 24 hrs and performed gene expression profiling using RNA-Seq. Control experiment were set up for both 8hr and 24hr treatment by treating the cells with ethanol only. We have done 2 biological replicate for each treatment.