Lipid Plays Likely Role in Malignant Pleural Mesothelioma and Cell Death

Lipid Plays Likely Role in Malignant Pleural Mesothelioma and Cell Death

A recent study suggests that a lipid named 1,2-Diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE) causes both cell injury/premature death and programmed cell death in malignant pleural mesothelioma (MPM) cells. The paper, entitled “Diarachidonoylphosphoethanolamine induces apoptosis of malignant pleural mesothelioma cells through a Trx/ASK1/p38 MAPK pathway,” was published in the Journal of Pharmacological Sciences.

MPM is an aggressive form of cancer that affects the protective lining of organs like the lung, heart, and abdominal cavity. Exposure to asbestos fibers is considered a major risk factor in the development of this disease, and asbestos has been suggested to induce DNA breakout and affect expression of certain genes involved in several enzymatic pathways.  Lipids based on phospholipid phosphatidylethanolamine are known to regulate a wide range of cellular processes. However,  little is known about the mechanism of their action and their involvement in cell injury, proliferation, programmed cell death, and the development of MPM.

In this study, the researchers explored the effect and mechanism of DAPE in inducing programmed cell death processes. To proceed, they carried out a series of in vitro experiments in cultured cells. To figure out how DAPE acts on these cells, antioxidants and inhibitors of NADPH oxidase involved in production of reactive oxygen species were used to prevent the effects of DAPE. Later, the cultured cells media were monitored by means of cell activity and enzymatic essays, and the data were statistically analyzed.

The results suggested that DAPE is responsible for the formation of reactive oxygen species and inhibition of activity of an enzyme named thioredoxin reductase, involved in preventing oxidative damage due to oxygen metabolism. DAPE releases a protein named ASK1 and activates another protein called p38 MAPK, both involved in oxidative stress and the development of cancer. It was also shown that p38 MAPK could be inhibited by antioxidants/inhibitors or by the elimination of ASK1. Cell death induced by DAPE could be prevented by eliminating ASK1.

Overall, these findings suggest that DAPE plays an important role in the generation of reactive oxygen species and the consecutive activation of the species ASK1 and p38 MAPK, both responsible in programmed cell death and the development of MPM.

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