Acylation with diangeloyl groups at C21-22 positions in triterpenoid saponins is essential for cytotoxicity towards tumor cells

Biochem Pharmacol. 2007 Feb 1;73(3):341-50. doi: 10.1016/j.bcp.2006.10.007. Epub 2006 Nov 7.

Abstract

Saponins are natural surfactants, found in many plants. Certain saponins are bioactive compounds with anticancer, antivirus and hemolytic activities. The mechanism is unknown. A saponin with antitumor activity was identified in Xanthoceras sorbifolia Bunge (Sapindaceae) and purified. This saponin is a triterpenoid saponin with a trisaccharide chain attached at C3 of the aglycone and two angeloyl groups acylated at C21 and C22. It inhibits the growth of tumor cells with IC50=2 microg/ml in OVCAR3 cells. To study the structure-activity relationship, the diangeloyl group or the carbohydrates of Xanifolia-Y were removed and tested for activity. It was found that removal of both angeloyl groups in C21 and C22 positions completely abolished its activity (IC50>120 microg/ml). However, when carbohydrates were remove, its activity was reduced but was not abolished (IC50=10 microg/ml). These results suggest that a presence of diangeloyl group in the triterpene structure play an essential role for activity. By comparison, compounds with a similar structure as Xanifolia-Y but have only one angeloyl group at C22: Xanifolia-X (IC50=6 microg/ml) or at C21: beta-escin (IC50=10 microg/ml), have less activity. Results suggest that diangeloyl group in both C21 and C22 positions are important contributing activity. Similar results were observed in hemolytic activity. It is concluded that acylation with angeloyl group at C21 and C22 positions of triterpenoid saponin is essential for its activity.

MeSH terms

  • Acylation
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Line, Tumor
  • Hemolysis / drug effects
  • Humans
  • Plant Extracts / pharmacology
  • Sapindaceae / chemistry*
  • Saponins / pharmacology*
  • Structure-Activity Relationship
  • Triterpenes / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • Saponins
  • Triterpenes