A potentially anti-metastatic agent in an approved medicinal honey formulation

Objectives: A significant improvement in pharmacological options is urgently required to meet the high standards of specificity and non-toxicity of modern medicines for cancer treatment. Honey is a natural product with an excellent nutritional profile and a wide range of anti-microbial, anti-oxidant, and probiotic activities that are largely used in traditional and complementary medicine. The present study aimed to evaluate the potential anti-neoplastic properties of a standardised, commercially available honey with approved dermatological and anti-inflammatory indications. Methods: The anti-proliferative, anti-metabolic, and anti-clonogenic activities of the honey were assessed in a panel of human and murine cell lines, including melanoma, lung, breast, colon and prostate cancer, and in spontaneously immortalised and human papilloma virus 16–transformed human keratinocyte lines. The in vitro effects of honey on intracellular reactive oxygen species generation, modulation of mitochondrial activity, cytoskeleton morphology, and anti-neoplastic activity in in vivo experimental tumours were also evaluated. Results: Experimental data indicated that Revamil© honey had a distinct anti-clonogenic activity, likely associated with a non-protidic, low-molecular-weight component, which was able to interact with a cell function shared by a panel of cell lines derived from tissues accounting for over 70% of the human tumour burden. This anti-clonogenic effect occurred along with a sharp induction of oxidative stress, acidification of intra-mitochondrial matrix, and severe derangement of cytoskeleton with cyto-chemical features of anoikis, and resulted in a strong suppression of cell mobility. In experimental tumours, a massive necrosis was induced. Conclusion: These preliminary results provide evidence that commercially available honey, registered with approved dermatological and complementary medicine indications, includes an unrecognised anti-neoplastic component potentially able to interfere with cellular mechanisms involved in the metastatic process.