Abstract
Aims: To assess the estrogenic activity of Manuka honey using the MCF7 cell proliferation assay.Study Design: In-vitro cell based E-screen.Place and Duration of Study: Ulster University, Coleraine, UK, September 2015 to September 2016.Methodology: Manuka honey (UMF15+) was characterized for total phenolic content (TPC) using the Folin-Ciocalteu assay and antioxidant power, using the 2, 2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) assay. Estrogenic activity was assessed using MCF-7 cells cultured in DMEM-F2 phenol red-free media supplemented with 10% charcoal stripped FBS and evaluated using Sulforhodamine B (SRB) colorimetric assay. All experiments were conducted in triplicate (n-12-48) and genistein was the positive control. The effect of Manuka honey (UMF15+) treatment on intracellular reactive oxygen species (ROS) was measured using the 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA) assay. Results: Manuka honey (UMF15+) antioxidant power was related to total phenols content. MCF7 growth promotion occurred at very low concentrations of honey (5x10-6-5x10-3% v/v honey; or 2.75 x10-10M - 2.75 x10-7 M TPC) indicative of estrogenic activity whilst higher concentrations of honey (>0.5% v/v) were inhibitory. Similarly, the genistein positive control demonstrated estrogenic activity indicated by MCF-7 cell growth at low concentrations (5x10-9-5x10-8 M) and toxicity at high concentrations. Estrogenic characteristics were quantified in terms of the relative proliferative potency (RPP) and relative proliferative effect (RPE) for Manuka honey of 18% and 22.5-27.5%, respectively. For genistein RPP was 0.1% and RPE was 70% compared to values of 100% for estradiol. Intracellular ROS increased for MCF-7 cells treated with increasing honey concentrations. Conclusion: Manuka honey (UMF15+) exhibits estrogenic activity monitored as growth promotion of MCF-7 breast cancer cells with estrogenic parameters being comparable to values reported for some purified flavonoids. Treatment of MCF-7 cells produced a dose-dependent rise in intracellular ROS.
Highlights
Breast cancer is the major cause of death globally amongst women accounting for 25% of all cancer and 10% cancer deaths in women [1]
Estrogenic characteristics were quantified in terms of the relative proliferative potency (RPP) and relative proliferative effect (RPE) for Manuka honey of 18% and 22.5-27.5%, respectively
Manuka honey (UMF15+) exhibits estrogenic activity monitored as growth promotion of MCF-7 breast cancer cells with estrogenic parameters being comparable to values reported for some purified flavonoids
Summary
Breast cancer is the major cause of death globally amongst women accounting for 25% of all cancer and 10% cancer deaths in women [1]. Alcohol consumption and obesity have been correlated to breast cancer risk, but attention is focusing on the possible role of environmental estrogens [1]. Circulating levels of estrogens and dysregulated estrogen signaling pathways are implicated in the development and progression of some breast cancers and for these, treatment is often aimed at the estrogen receptor signaling pathway. One of the most common chemotherapeutic drugs in the treatment of estrogen receptor positive breast cancer since the 1980s, blocks the estrogenic effects on breast cancer cells [4]. Some breast cancer patients may show resistance to tamoxifen treatment increased dosage can lead to increasing risks of side-effects on normal tissues [5]. A diminished effect of chemotherapeutic agents has invited research into the role of alternative treatments and adjuvants in breast cancer treatment
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