The mechanism of action of plitidepsin.
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.
Muñoz-Alonso
Maria J
MJ
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Arturo Duperier, 4, E-28029 Madrid, Spain.
González-Santiago
Laura
L
Martínez
Teresa
T
Losada
Alejandro
A
Galmarini
Carlos M
CM
Muñoz
Alberto
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002986:Clinical Trials as Topic; D047630:Depsipeptides / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010456:Peptides, Cyclic; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C098980:plitidepsin