Intravenous Administration of Manuka Honey Inhibits TumorGrowth and Improves Host Survival When Used in Combination with Chemotherapy ina Melanoma Mouse ModelPLoS ONEManuka honey has been recognized for its anti-bacterial andwound-healing activity but its potential antitumor effect is poorly studieddespite the fact that it contains many antioxidant compounds. In this study, we investigated the antiproliferativeactivity of manuka honey on three different cancer cell lines, murine melanoma(B16.F1) and colorectal carcinoma (CT26) as well as human breast cancer (MCF-7)cells in vitro. The data demonstrate that manuka honey has potentanti-proliferative effect on all three cancer cell lines in a time- anddose-dependent manner, being effective at concentrations as low as 0.6% (w/v).This effect is mediated via the activation of a caspase 9-dependent apoptoticpathway, leading to the induction of caspase 3, reduced Bcl-2 expression, DNAfragmentation and cell death. Combination treatment of cancer cells with manukaand paclitaxel in vitro, however, revealed no evidence of a synergistic actionon cancer cell proliferation. Furthermore, we utilized an in vivo syngeneicmouse melanoma model to assess the potential effect ofintravenously-administered manuka honey, alone or in combination withpaclitaxel, on the growth of established tumors. Our findings indicate that systemic administration of manukahoney was not associated with any alterations in haematological or clinicalchemistry values in serum of treated mice, demonstrating its safety profile. Treatment with manuka honey alone resulted in about 33%inhibition of tumor growth, which correlated with histologically observableincrease in tumor apoptosis. Although better control of tumor growth wasobserved in animals treated with paclitaxel alone or in combination with manukahoney (61% inhibition), a dramatic improvement in host survival was seen in theco-treatment group. This highlights a potentially novel role for manuka honey inalleviating chemotherapy-induced toxicity.
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