Abstract
The prognosis for men diagnosed with advanced metastatic prostate cancer is poor. A low five-year survival rate of 28% highlights the ongoing need for improved treatment options, with attention to a reduction in prostate cancer metastasis.
Honey bee (Apis mellifera) products have been recognised for their medicinal properties for thousands of years, with both honey and bee venom having been used to treat wounds and rheumatoid arthritis. However, only within the last 30 years have honey bee products been investigated for the treatment of cancer. Of the over 200 constituents in honey, phenolic compounds, which include flavonoids and phenolic acids, have been suggested to be responsible for most of the beneficial properties. In addition, bee venom and melittin have been shown to possess anti-cancer effects towards many cell types including prostate. The cytotoxicity of both honey and bee venom have been reported previously in many cancer cell lines, including prostate cancer; however, their anti-metastatic effects are not well documented.
The present study was carried out to examine the in vitro anti-metastatic activity of three New Zealand honeys, honey-derived phenolic compounds, and bee venom against the PC3 prostate cancer cell line. Cytotoxicity was assessed using both colourimetric and dye exclusion assays to determine maximal non-lethal concentrations. Quantification of phenolic compounds in the three New Zealand honeys was made using HPLC. Finally, anti-metastatic effects were assessed in PC3 cells using multiple techniques including adhesion assays, scratch wound-healing assays, and Boyden chamber migration and invasion assays.
Honey, quercetin, and the bee venom extract melittin, caused a reduction in cell adhesion, while other phenolic compounds, over a wide range of concentrations, had no effect. Thyme and honeydew honey inhibited migration over 48 h, although manuka did not. However, all honeys inhibited invasion between 50 - 75% over 72 h. Of the five honey-derived phenolic compounds selected, only caffeic acid did not affect cell migration, and only kaempferol did not inhibit invasion. Finally, melittin inhibited both migration and invasion by 60% and 50%, respectively.
These results showed that honey could reduce the migration and invasion of prostate cancer cells and that the anti-metastatic properties of honey may be attributed to the presence of phenolic compounds. Further, the bee venom extract melittin, could also reduce the migration and invasion of prostate cancer cells. Honey and melittin may be beneficial for the prevention of prostate cancer metastasis, and therefore co-administration with chemotherapeutic agents should be investigated. However, due to the variability of phenolic compounds in honeys of different floral origins, standardisation or supplementation of honey may be recommended.