title: Inhibition of Gli/hedgehog signaling in prostate cancer cells by "cancer bush" Sutherlandia frutescens extract.
abstract: Sutherlandia frutescens is a medicinal plant, traditionally used to treat various types of human diseases, including cancer. Previous studies of several botanicals link suppression of prostate cancer growth with inhibition of the Gli/hedgehog (Gli/Hh) signaling pathway. Here we hypothesized the anti-cancer effect of S. frutescens was linked to its inhibition of the Gli/Hh signaling in prostate cancer. We found a dose- and time-dependent growth inhibition in human prostate cancer cells, PC3 and LNCaP, and mouse prostate cancer cell, TRAMP-C2, treated with S. frutescens methanol extract (SLE). We also observed a dose-dependent inhibition of the Gli-reporter activity in Shh Light II and TRAMP-C2QGli cells treated with SLE. In addition, SLE can inhibit Gli/Hh signaling by blocking Gli1 and Ptched1 gene expression in the presence of a Gli/Hh signaling agonist (SAG). A diet supplemented with S. frutescens suppressed the formation of poorly differentiated carcinoma in prostates of TRAMP mice. Finally, we found Sutherlandioside D was the most potent compound in the crude extract that could suppress Gli-reporter in Shh Light II cells. Together, this suggests that the S. frutescens extract may exert anti-cancer effect by targeting Gli/Hh signaling, and Sutherlandioside D is one of the active compounds.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Key Laboratory of Animal Reproductive Physiology & Embryo Technology, Ministry of Agriculture, Yangling, Shaanxi, 712100, China.|Department of Biochemistry, University of Missouri, Columbia, Missouri, 65211, USA.|MU Center for Botanical Interaction Studies, University of Missouri, Columbia, Missouri, 65211, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Lin
authors.affiliation: MU Center for Botanical Interaction Studies, University of Missouri, Columbia, Missouri, 65211, USA.|Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri, 65211, USA.|Department of Veterinary Technology, Nebraska College of Technical Agriculture, Curtis, Nebraska, 69025, USA.
authors.forename: Glenn A
authors.initials: GA
authors.lastname: Jackson
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, Missouri, 65211, USA.|MU Center for Botanical Interaction Studies, University of Missouri, Columbia, Missouri, 65211, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, Missouri, 65211, USA.|MU Center for Botanical Interaction Studies, University of Missouri, Columbia, Missouri, 65211, USA.
authors.forename: Sara K
authors.initials: SK
authors.lastname: Drenkhahn
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, Missouri, 65211, USA.|MU Center for Botanical Interaction Studies, University of Missouri, Columbia, Missouri, 65211, USA.|Institute of Biological Chemistry, Washington State University, Pullman, Washington, 99164, USA.
authors.forename: Korey J
authors.initials: KJ
authors.lastname: Brownstein
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, Missouri, 65211, USA.|MU Center for Botanical Interaction Studies, University of Missouri, Columbia, Missouri, 65211, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Starkey
authors.affiliation: MU Center for Botanical Interaction Studies, University of Missouri, Columbia, Missouri, 65211, USA.|Department of Animal Sciences, University of Missouri, Columbia, Missouri, 65211, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Lamberson
authors.affiliation: MU Center for Botanical Interaction Studies, University of Missouri, Columbia, Missouri, 65211, USA.|Department of Animal Sciences, University of Missouri, Columbia, Missouri, 65211, USA.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Fritsche
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, Missouri, 65211, USA.|MU Center for Botanical Interaction Studies, University of Missouri, Columbia, Missouri, 65211, USA.
authors.forename: Valeri V
authors.initials: VV
authors.lastname: Mossine
authors.affiliation: MU Center for Botanical Interaction Studies, University of Missouri, Columbia, Missouri, 65211, USA.|Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri, 65211, USA.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Besch-Williford
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, Missouri, 65211, USA.|MU Center for Botanical Interaction Studies, University of Missouri, Columbia, Missouri, 65211, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Folk
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Key Laboratory of Animal Reproductive Physiology & Embryo Technology, Ministry of Agriculture, Yangling, Shaanxi, 712100, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, Missouri, 65211, USA.|MU Center for Botanical Interaction Studies, University of Missouri, Columbia, Missouri, 65211, USA.
authors.forename: Dennis B
authors.initials: DB
authors.lastname: Lubahn
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D007887:Fabaceae / Q000737:chemistry; D015870:Gene Expression; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D010936:Plant Extracts / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D015398:Signal Transduction; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D000071676:Zinc Finger Protein GLI1
chemical_list: D000970:Antineoplastic Agents; C400551:GLI1 protein, human; C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D010936:Plant Extracts; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1
keywords: Sutherlandia frutescens; prostate cancer; sonic hedgehog