Abstract
Manuka honey has been recognized for its anti-bacterial and wound-healing activity but its potential antitumor effect is poorly studied despite the fact that it contains many antioxidant compounds. In this study, we investigated the antiproliferative activity 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 potent anti-proliferative effect on all three cancer cell lines in a time- and dose-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 apoptotic pathway, leading to the induction of caspase 3, reduced Bcl-2 expression, DNA fragmentation and cell death. Combination treatment of cancer cells with manuka and paclitaxel in vitro, however, revealed no evidence of a synergistic action on cancer cell proliferation. Furthermore, we utilized an in vivo syngeneic mouse melanoma model to assess the potential effect of intravenously-administered manuka honey, alone or in combination with paclitaxel, on the growth of established tumors. Our findings indicate that systemic administration of manuka honey was not associated with any alterations in haematological or clinical chemistry 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 observable increase in tumor apoptosis. Although better control of tumor growth was observed in animals treated with paclitaxel alone or in combination with manuka honey (61% inhibition), a dramatic improvement in host survival was seen in the co-treatment group. This highlights a potentially novel role for manuka honey in alleviating chemotherapy-induced toxicity.
Highlights
Honey has been used for more than 2000 years as traditional medicine in different cultures, for its wound healing properties
Manuka inhibits growth of cancer cells The potential effect of manuka on cancer cell proliferation was investigated using three tumor cell lines differing in type and origin, the murine melanoma (B16.F1) and colon carcinoma (CT26) cells and the human breast cancer (MCF-7) cell line
Similar results were observed with the CT26 and MCF-7 cancer cell lines
Summary
Honey has been used for more than 2000 years as traditional medicine in different cultures, for its wound healing properties. Intrinsic properties of honey like high osmolarity and acidity, as well as the presence of flavonoids and phenolic acids are responsible for its antibacterial and antioxidant activities [1]. While manuka honey shares constituents, e.g. glucose-oxidases, with other honeys it contains other phytochemical factors that potentiate its antibacterial activity like methylglyoxal [6]. A 5.8 kD, heat-sensitive, proteaseresistant, component, that was devoid of any antibacterial activity was identified to be responsible for the induction of cytokine production via interaction with TLR4 on macrophages [11]. These studies suggest the presence of unique, yet-to-be-characterized, constituents with desired activities in manuka honey. An investigation of the anti-proliferative properties of manuka honey has not been undertaken
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