Novel effects of glycyrrhetinic acid on the central nervous system tumorigenic progenitor cells: induction of actin disruption and tumor cell-selective toxicity

Eur J Med Chem. 2010 Jul;45(7):2943-8. doi: 10.1016/j.ejmech.2010.03.021. Epub 2010 Mar 25.

Abstract

Licorice extracts are used worldwide in foods and medicines, and glycyrrhetinic acid (GA) is a licorice component that has been reported to induce various important biological activities. In the present study, we show that GA induces actin disruption and has tumor cell-selective toxic properties, and that its selectivity is superior to those of all the clinically available antitumor agents tested. The cytotoxic activity of GA and the tested antitumor agents showed better correlation with the partition coefficient (log P) values rather than the polar surface area (PSA) values. For selective toxicity against tumor cells, GA was most effective at 10 microM that was the same concentration as the previously reported maximum plasma GA level reached in humans ingesting licorice. These results suggest that GA could be utilized as a promising chemopreventive and therapeutic antitumor agent. The underlying mechanisms involved in the selective toxicity to tumor cells by GA are also preliminarily discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / toxicity
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Central Nervous System / pathology*
  • Genes, myc / genetics
  • Genes, ras / genetics
  • Glycyrrhetinic Acid / pharmacology*
  • Glycyrrhetinic Acid / toxicity
  • Humans
  • Mice
  • Neoplasms / pathology*
  • Stem Cells / drug effects*
  • Stem Cells / metabolism
  • Stem Cells / pathology*
  • Transfection

Substances

  • Actins
  • Antineoplastic Agents
  • Glycyrrhetinic Acid