Red propolis: Anticancer mechanism probed

Medicinal propolis

Propolis has a range of renowned medicinal properties and has been used to treat bacteria, viruses, fungal infections and gastrointestinal problems. One more string to the bow of this resin, produced by bees as a glue to block up unwanted gaps in the hive and protect the entrance, is its anticancer activity which has been demonstrated on a number of different cancers including leukaemia and bladder, breast and pancreatic cancer.

In South America, one type of propolis is produced exclusively when bees collect resin from the coinvine (Dalbergia ecastophyllum). Known as red propolis, it is found in the northeastern region of Brazil and it, too, has been credited with the ability to kill cancer cells. The mechanism by which red propolis acts is unclear, but it is rich in flavonoids and phenolic acids, as a team of researchers in Brazil established by high resolution mass spectrometry.

Many of these compounds have been attributed with health-promoting properties but they still cannot explain how the anticancer mechanism operates. So, the same team has undertaken a proteomics investigation to see which proteins are affected by red propolis and whether they can throw any light on its mode of action.

Cancer cultures

Mariana Roesch-Ely and coworkers from the University of Caxias do Sul added propolis extract to two cell cultures, one of benign human epithelial embryonic kidney cells (Hek-293) and the other human laryngeal epidermoid carcinoma cells. Control cultures of each were also grown using an aqueous ethanol solution as the additive.

The proteins were subsequently extracted and broken up into their constituent peptides using the enzyme trypsin. The peptides were analysed by LC/MS using tandem mass spectrometry and the results were used to identify their proteins, the changes in abundance being measured and compared with the controls for the two cultures.

The Hek-293 cells yielded a total of 773 identified proteins but far more were found and quantified in the Hep-2 cancer cells with a total of 1336. The distributions of the molecular functions were remarkably similar between the different types of cells, dominated by catalytic activity, protein binding and structural molecule activity.

However, the main proteins of interest were those that were differentially expressed between the cultures treated with red propolis and the corresponding controls, 16 being identified for the Hep-2 line and four for the Hek-293 line.

Propolis affects proteins

The altered Hep-2 proteins comprised 14 that were lowered in abundance and two that were up-regulated. They belonged to a number of different classes and were found in various subcellular locations. All of the affected proteins have been associated in the literature with the cell signalling mechanisms involved in cancer.

Four cytoskeletal proteins were down-regulated, including talin-1 which has been considered a biomarker for hepatocellular cancer in which it is elevated. Epiplakin has also been reported to be up-regulated in other cancers even though it was down-regulated in this study.

Other differentially regulated proteins were associated with different types of cancer too but were not always affected the same way, some being up-regulated in the reported cancers but down-regulated after propolis treatment. The researchers postulated that, for some proteins, this might be due to the action of red propolis returning the proteins back to their normal abundances.

In future work, they intend to isolate major compounds from the propolis extract and add them to cancer cell cultures to see what effects they might have on particular proteins. This might lead to the development of new cancer drugs. In the meantime, the current work provides more evidence to sift through in an effort to define how the anticancer effects of red propolis work at the molecular level.

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