In vitro antiproliferative/cytotoxic activity on cancer cell lines of a cardanol and a cardol enriched from Thai Apis mellifera propolis

<p>Abstract</p> <p>Background</p> <p>Propolis is a complex resinous honeybee product. It is reported to display diverse bioactivities, such as antimicrobial, anti-inflammatory and anti-tumor properties, which are mainly due to phenolic compounds, and especially flavonoids. The diversity of bioactive compounds depends on the geography and climate, since these factors affect the floral diversity. Here, <it>Apis mellifera </it>propolis from Nan province, Thailand, was evaluated for potential anti-cancer activity.</p> <p>Methods</p> <p>Propolis was sequentially extracted with methanol, dichloromethane and hexane and the cytotoxic activity of each crude extract was assayed for antiproliferative/cytotoxic activity <it>in vitro </it>against five human cell lines derived from duet carcinoma (BT474), undifferentiated lung (Chaco), liver hepatoblastoma (Hep-G₂), gastric carcinoma (KATO-III) and colon adenocarcinoma (SW620) cancers. The human foreskin fibroblast cell line (Hs27) was used as a non-transformed control. Those crude extracts that displayed antiproliferative/cytotoxic activity were then further fractionated by column chromatography using TLC-pattern and MTT-cytotoxicity bioassay guided selection of the fractions. The chemical structure of each enriched bioactive compound was analyzed by nuclear magnetic resonance and mass spectroscopy.</p> <p>Results</p> <p>The crude hexane and dichloromethane extracts of propolis displayed antiproliferative/cytotoxic activities with IC₅₀values across the five cancer cell lines ranging from 41.3 to 52.4 μg/ml and from 43.8 to 53.5 μg/ml, respectively. Two main bioactive components were isolated, one cardanol and one cardol, with broadly similar <it>in vitro </it>antiproliferation/cytotoxicity IC₅₀values across the five cancer cell lines and the control Hs27 cell line, ranging from 10.8 to 29.3 μg/ml for the cardanol and < 3.13 to 5.97 μg/ml (6.82 - 13.0 μM) for the cardol. Moreover, both compounds induced cytotoxicity and cell death without DNA fragmentation in the cancer cells, but only an antiproliferation response in the control Hs27 cells However, these two compounds did not account for the net antiproliferation/cytotoxic activity of the crude extracts suggesting the existence of other potent compounds or synergistic interactions in the propolis extracts_.</p> <p>Conclusion</p> <p>This is the first report that Thai <it>A. mellifera </it>propolis contains at least two potentially new compounds (a cardanol and a cardol) with potential anti-cancer bioactivity. Both could be alternative antiproliferative agents for future development as anti-cancer drugs.</p

The Chemical and Biological Properties of Propolis

The term propolis comes from two Greek words, pro (which means for or in defence of) and polis (which means the city); thus, propolis means in defence of the city or beehive. Propolis is a sticky resinous substance, which is gathered from buds and the bark of trees. It is also known as "bee glue" as bees use it to cover surfaces, seal holes and close gaps in their hives, thus providing a sterile environment that protects them from microbes and spore-producing organisms, including fungi and molds. It can be considered to be a potent chemical weapon against bacteria, viruses, and other pathogenic microorganisms that may invade the bee colony. Also, bees use propolis as an embalming substance, to mummify invaders such as other insects, that have been killed and are too heavy to remove from the colony. Thus, propolis is important for bee health but it also has activity against many human diseases. It is a powerful anti-oxidant and can modulate the activity of reactive oxygen species within the human body. The most studied aspect of propolis is its anti-bacterial activity, which is almost always present at a moderate to high level depending on the exact type of propolis. It is in general more active against Gram positive than Gram negative bacteria, but activity against Gram negative bacteria has been observed. Propolis has been found to be active against a range of viruses and also is almost always active against protozoa such as Tryanosoma brucei and Leishmania donovani. Propolis also shows activity against cardiovascular diseases and diabetes and has immunomodulatory effects. Anti-cancer activity has also been observed. In summary, propolis is remarkable for its range of biological activities and for the variety of its chemical composition. It may be of great importance both to bees and humans