Mezerein is a toxic diterpene ester found in the sap of Daphne mezereum and related plants.

Plants of the genera Euphorbiaceae and Thymelaeaceae possess a wide variety of different phorbol esters, which share the capacity of mimicking diacylglycerol (DAG) and thus activating different isoforms of protein kinase C. Mezerein was first isolated in 1975.

It has antileukemic properties in mice, but it is also defined as a weak promoter of skin cancers in the same species.

[2] All parts of the plants contain an acrid and irritant sap that contains mezerein, thought to be the principal poison.

When a large dose is taken, there can be shivering, dilation of the pupils, damage to the oral passages and the intestine and even death.

They are both PKC activators but with a different selectivity: mezerein exhibits antileukemic properties while daphnetoxin does not.

In the last stage, progression, the tumor has become karyotypically instable: morphological changes in the normal chromosomal structure take place.

Protein kinase C controls the cell cycle, so chemicals that interact with it can have pro-proliferative or anti-proliferative effects.

Now, PKC can phosphorylate various substrates, affecting the activity of several intracellular pathways that regulate cell cycle and apoptosis among others.

PKC binding to the plasma membrane is reversible, because after a short period of time DAG is enzymatically degraded, causing PKC to undergo a conformational change and detach from the membrane and stop phosphorylating substrates.

This causes overstimulation of the pathways PKC initiates, leading to more cellular proliferation and less apoptosis.

Furthermore, high doses of mezerein have been used to terminally differentiate cancer cells, preventing their growth.

[12][13] Mezerein has been shown to have two effects in chick embryo fibroblasts (CEF cells) that are associated with cancer.