Mezerein
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| Other names
meserein; 12β-[(E,E)-5-Phenyl-2,4-pentadienoyloxy]daphnetoxin; daphnetoxin,12-[(1-oxo-5-phenyl-2,4-pentadienyl)oxy]-,12-beta(E,E)]
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| Identifiers | |
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3D model (JSmol)
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| 1675867 | |
| ChemSpider | |
| ECHA InfoCard | 100.159.782 |
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PubChem CID
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| Properties | |
| C38H38O10 | |
| Molar mass | 654.71 g·mol−1 |
| Melting point | 258.0 to 262.0 °C; 496.4 to 503.6 °F; 531.1 to 535.1 K |
| Hazards | |
| R-phrases (outdated) | R38, |
| S-phrases (outdated) | S22,S23,S24, S25 |
| NFPA 704 | |
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Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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 (what is   ?) |
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| Infobox references | |
Mezerein is a toxic diterpene ester found in the sap of Daphne mezereum and related plants. Plants of the genus 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. All parts of the plants contain an acrid and irritant sap that contains mezerein, thought to be the principal poison. The sap is especially prevalent in the bark and berries.
Mezerein is highly liposoluble and can cause vomiting, diarrhea and burning of the mouth. 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. It can also irritate the skin, resulting in redness by slight damage of the veins. Because of causing this redness, the sap used to be applied as rouge.
Mezerein can be found in Daphne mezereum. This plant has been used to make dyes, treat rheumatism and indolent ulcers and as a cosmetic. In homeopathy, the plant is used to treat primarily skin disorders but is also prescribed to treat anxiety related to digestive disorders and congestion. Once the toxicity of the plant was discovered, these uses were abandoned. The toxicity also led to new uses. In extreme cases, the berries are used to commit suicide.
The toxins mezerein and daphnetoxin are both present in the Daphne genus. Daphnetoxin has a structure similar to Mezerein, with the phenyl-pentadienoyl component (top left of the Mezerein structural diagram) missing. They are both PKC activators but with a different selectivity: mezerein exhibits antileukemic properties while daphnetoxin does not.
Mezerein is a second stage tumor promoter. According to the IPP model, tumorigenesis happens in three stages: initiation, promotion, and progression. In the first stage, initiation, a gene-mutation with change of function occurs. These mutations often occur in oncogenes or regulatory sequences. In the promotion stage, interaction with cellular signaling pathways takes place. This leads to growth advantage for initiated cells. In the last stage, progression, the tumor has become karyotypically instable: morphological changes in the normal chromosomal structure take place. This instability is caused by additional mutations. This leads to metastasis, hyperproliferation and loss of control by the cellular environment. There is an increased risk that the tumor cells will mutate other genes. Second stage tumor promoters like mezerein do not have the capacity to initiate tumors, but can create circumstances in which initiated cells are more susceptible to additional mutations or in which initiated cells have growth advantage. They do not cause mutations themselves: promotion happens through interference with cellular signaling pathways.
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Wikipedia