title: Inhibition of matrix metalloproteinases related to metastasis by diosgenyl and pennogenyl saponins.
abstract: BACKGROUND
  Diosgenyl and pennogenyl saponins isolated from Rhizoma Paridis, showed pro-apoptosis and immunoregulation with antitumor activity in cultured cells and animal systems.
  
  
  OBJECTIVE
  To evaluate their anti-metastatic mechanism on cancer cells and discuss their structure-activity relationship on anti-tumor effect.
  
  
  METHODS
  This research used the wound healing and migration assay to detect their anti-invasive effect on B16 melanoma cells. Through the gelatin zymography assay, immunofluorescence analysis and western blot, saponins exhibited different levels of protein expression inhibition of MMP-1, -2, -3, -9 and -14.
  
  
  RESULTS
  Through the analysis, diosgenyl and pennogenyl saponins inhibited the metastasis of B16 melanoma cells. Diosgenyl saponins also showed strong suppression of enzyme activity of MMP-2 and -9. Different saponins exhibited different levels of inhibition on MMP expression.
  
  
  CONCLUSIONS
  17-α OH increases the sensitivity of diosgenyl saponins to the membrane-bound protease which can stimulate proMMP-2 activation, but it also decreases the anti-metastatic activity of diosgenyl saponin. Furthermore, their combination might provide a potential therapeutic modality for metastasis.
authors.affiliation: School of Pharmaceutical Science and Technology, Tianjin University, Weijin Road, Tianjin 300072, China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Man
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Gao
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Yan
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Changxiao
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D029064:Araceae / Q000737:chemistry; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008546:Melanoma, Experimental / Q000201:enzymology* / Q000556:secondary; D051379:Mice; D015394:Molecular Structure; D010946:Plants, Medicinal; D011480:Protease Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D012503:Saponins; D020782:Matrix Metalloproteinases