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. Epub 2015 Oct 6.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Fabaceae / chemistry
  • Gene Expression
  • Hedgehog Proteins / antagonists & inhibitors*
  • Humans
  • Kruppel-Like Transcription Factors / antagonists & inhibitors*
  • Male
  • Mice
  • Mice, Inbred A
  • Plant Extracts / pharmacology*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Random Allocation
  • Signal Transduction
  • Transcription Factors / antagonists & inhibitors*
  • Zinc Finger Protein GLI1

Substances

  • Antineoplastic Agents
  • GLI1 protein, human
  • Gli1 protein, mouse
  • Hedgehog Proteins
  • Kruppel-Like Transcription Factors
  • Plant Extracts
  • Transcription Factors
  • Zinc Finger Protein GLI1