The mechanism of action of plitidepsin

Curr Opin Investig Drugs. 2009 Jun;10(6):536-42.

Abstract

Plitidepsin (PharmaMar SA) is a cyclodepsipeptide originally isolated from the Mediterranean tunicate Aplidium albicans, and has demonstrated strong anticancer activity against a large variety of cultured human cancer cells and in xenografted mice. Phase I/II clinical trials of plitidepsin yielded promising results of anticancer activity in patients with cancer. Several studies have revealed that plitidepsin induces cell cycle arrest or apoptosis in a cell type- and dose-dependent manner. These effects are related to the induction of early oxidative stress, the activation of Rac1 GTPase and the inhibition of protein phosphatases, which in conjunction cause the sustained activation of JNK and p38 MAPK. This review outlines the current knowledge of plitidepsin activity, with a primary focus on the molecular mechanisms of action of the compound.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Clinical Trials as Topic
  • Depsipeptides / pharmacology*
  • Depsipeptides / therapeutic use
  • Humans
  • Models, Biological
  • Neovascularization, Physiologic / drug effects
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Depsipeptides
  • plitidepsin