Inhibition of Gli/hedgehog signaling in prostate cancer cells by "cancer bush" Sutherlandia frutescens extract

  • Cell Biol Int. 2016 Feb;40(2):131-42. doi: 10.1002/cbin.10544.
Hui Lin  1  2  3 ,  Glenn A Jackson  3  4  5 ,  Yuan Lu  2  3 ,  Sara K Drenkhahn  2  3 ,  Korey J Brownstein  2  3  6 ,  Nicholas J Starkey  2  3 ,  William R Lamberson  3  7 ,  Kevin L Fritsche  3  7 ,  Valeri V Mossine  2  3 ,  Cynthia L Besch-Williford  3  4 ,  William R Folk  2  3 ,  Yong Zhang  1 ,  Dennis B Lubahn  2  3
Affiliations
  • 1. College of Veterinary Medicine, Northwest A&F University, Key Laboratory of Animal Reproductive Physiology & Embryo Technology, Ministry of Agriculture, Yangling, Shaanxi, 712100, China.
  • 2. Department of Biochemistry, University of Missouri, Columbia, Missouri, 65211, USA.
  • 3. MU Center for Botanical Interaction Studies, University of Missouri, Columbia, Missouri, 65211, USA.
  • 4. Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri, 65211, USA.
  • 5. Department of Veterinary Technology, Nebraska College of Technical Agriculture, Curtis, Nebraska, 69025, USA.
  • 6. Institute of Biological Chemistry, Washington State University, Pullman, Washington, 99164, USA.
  • 7. Department of Animal Sciences, University of Missouri, Columbia, Missouri, 65211, USA.
PMID: 26377232 DOI: 10.1002/cbin.10544
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.

Keywords
Sutherlandia frutescens; prostate cancer; sonic hedgehog.
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