Soybean saponin inhibits tumor cell metastasis by modulating expressions of MMP-2, MMP-9 and TIMP- 2

Cancer Lett. 2008 Mar 8;261(1):84-92. doi: 10.1016/j.canlet.2007.11.006. Epub 2007 Dec 20.

Abstract

The antimetastatic properties of soybean saponin were investigated by evaluating matrix metalloproteinase (MMP-2 and MMP-9) production in HT-1080 cells. The mRNA expression levels of MMP-2 and MMP-9 were determined by RT-PCR analysis. The levels of secreted MMP-2, MMP-9 and tissue inhibitor of metalloproteinase-2 (TIMP-2) were determined by gelatin zymography and/or ELISA. The invasion of a Matrigel-coated membrane by human fibrosarcoma HT-1080 and HT-29 colon cancer cells was quantitatively assessed by counting the migrated cells. The treatment of HT-1080 cells with soybean saponin inhibited the mRNA expression of and reduced the amounts of secreted MMP-2 and MMP-9, whereas it increased the amount of secreted TIMP-2 dose-dependently. Soybean saponin significantly inhibited the invasion of HT-1080 cells through a Matrigel-coated membrane. The antimetastatic properties by soybean saponin were further confirmed by in vivo mice experiment via the tail vein injection of CT-26 colon cancer cells after feeding the mice the dietary soybean saponin. The incidence of metastatic tumor colonization of lungs of mice moderately decreased 2 weeks after the tail vein injection of CT-26 cells. Our current data support the notion that soybean saponin inhibits tumor cell metastasis by suppressing MMP-2 and MMP-9 productions, and stimulating TIMP-2 secretion, thereby suggesting that soybean saponin has a chemopreventive property against cancer metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Colonic Neoplasms / enzymology*
  • Colonic Neoplasms / pathology
  • Fibrosarcoma / enzymology*
  • Fibrosarcoma / pathology
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Glycine max / chemistry*
  • HT29 Cells
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinases / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Metastasis / prevention & control*
  • Neoplasm Transplantation
  • Saponins / pharmacology*
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism

Substances

  • Saponins
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9