In a recent study published in the Nutrients , a group of researchers evaluated the antitumor activity of Manuka honey (MH) on human breast cancer (BC) cells and its underlying molecular mechanisms in both in vitro and in vivo preclinical models. Background BC remains a leading cause of death among women worldwide. Despite the effectiveness of endocrine therapy in treating estrogen receptor (ERα)-positive BC, resistance to treatment often develops, especially in metastatic cases.
Further research is needed to understand the mechanisms behind MH's antitumor effects fully and to evaluate its potential as a viable treatment option for breast cancer in clinical settings. About the study MH Methylglyoxal (MGO) 550+ and dehydrated MH powder were provided by Manuka Health New Zealand Limited. Stock solutions of the MH cyclopower powder were prepared by dissolving aliquots in a 15% ethanol/Hanks’ balanced salt solution buffer.
As controls, 5% dextrose and 5% Mesquite honey were used, along with W6 Cavamax, an α-cyclodextrin powder involved in the MH cyclopower powder's manufacture. All substances were dissolved in a cell culture medium as w/v solutions. Human BC cell lines were sourced from the American Type Culture Collection (ATCC) and cultured according to their guidelines.
ERα-positive Michigan Cancer Foundation (MCF-7) cells were cultured in Dulbecco's Modified Eagle Medium (DMEM) or Roswell Park Memorial Institute Medium 1640 (RPMI-1640) media, while triple-negative M.D. Anderson - Metastatic Breast 231 (MDA-MB-231) (a breast cancer cell line) cells were cultured in RPMI-1640, both supplemented with 10% fetal bovine serum and antibiotics.
Additional cell lines, including human non-small cell lung cancer and pancreatic cancer cells, were also obtained from ATCC and maintained in RPMI 1640 with 10% FBS. Control human mammary epithelial cells (HMEC) were sourced from Invitrogen/ThermoFisher Scientific. Cell proliferation was assessed using colorimetric assays after treating cells with various concentrations of the substances.
For protein analysis, Western blotting was performed on MCF-7 cells treated with MH, using specific antibodies for proteins involved in the pathways of interest. Apoptosis was evaluated in treated cells using an Annexin V staining assay, followed by flow cytometry. In vivo, human MCF-7 cells were injected into nude mice, with treatments administered via oral gavage.
Tumor volumes were measured and analyzed statistically to determine the treatment effects. Statistical analyses were performed using Student’s t-test and Analysis of Variance (ANOVA), with significance set at p < 0.05.
Study results MH has shown significant antitumor effects in human BC cancer cells. In vitro studies demonstrated that MH, at concentrations ranging from 0.3% to 5.
0%, significantly inhibited the proliferation of ERα-positive MCF-7 breast cancer cells in a dose-dependent manner. This effect was stronger in MCF-7 cells compared to triple-negative MDA-MB-231 cells, which showed a more modest response. Related Stories New trial explores BAFF CAR T-cell therapy for relapsed myeloma Advancements in neoantigen vaccines offer hope for personalized cancer therapy New research gives unprecedented view of colorectal cancer genetic makeup Similar antiproliferative effects were observed when MCF-7 cells were treated with dehydrated MH powder.
Additionally, MH significantly reduced the proliferation of H2110 non-small cell lung cancer and PANC1 pancreatic cancer cells, both of which express aromatase and estrogen receptors. The combination of MH with tamoxifen, a commonly used antiestrogen therapy, was also assessed. MH alone significantly inhibited MCF-7 cell proliferation without affecting non-malignant HMECs.
When combined with tamoxifen, MH further enhanced the suppression of MCF-7 cell proliferation, suggesting a potential role for MH in overcoming tamoxifen resistance in BC treatment. Further investigations into the mechanism of MH's antitumor effects revealed that MH induces apoptosis in MCF-7 cells, as evidenced by increased Annexin V staining and Poly (ADP-Ribose) Polymerase (PARP) cleavage. The apoptotic response was more pronounced in MCF-7 cells than in MDA-MB-231 cells, indicating a selective action of MH on ER-positive breast cancer cells.
These pro-apoptotic effects were independent of MH's sugar content, as neither dextrose nor Mesquite honey, another honey variant, produced similar results. MH also activated AMP-activated protein kinase (AMPK) and inhibited the Phosphoinositide 3-Kinase / Protein Kinase B (also known as AKT) / Mechanistic Target of Rapamycin (PI3K/AKT/mTOR) signaling pathway, which is critical in regulating cell growth and survival. Additionally, MH treatment reduced the phosphorylation of Signal Transducer and Activator of Transcription 3 (STAT3), a transcription factor involved in tumor progression and inflammation, further supporting MH's role in disrupting cancer cell survival mechanisms.
In vivo studies using a Human BC xenograft model in nude mice corroborated these findings. MH treatment, administered via oral gavage, significantly suppressed the growth of MCF-7 tumors compared to control-treated mice, demonstrating MH's potential to inhibit tumor progression in a living organism. Conclusions To summarize, this study explored the impact of MH on human BC cells using both in vitro and in vivo models.
The results showed that MH significantly inhibited tumor cell proliferation and induced apoptosis in ER-positive MCF-7 cells, with less pronounced effects in triple-negative MDA-MB-231 cells. In vivo, orally administered MH significantly reduced the growth of breast tumor xenografts in mice, highlighting its potential as an anticancer or chemopreventive agent. Márquez-Garbán DC, Yanes CD, Llarena G, et al.
Manuka Honey Inhibits Human Breast Cancer Progression in Preclinical Models. Nutrients . (2024) doi: https://doi.
org/10.3390/nu16142369 https://www.mdpi.
com/2072-6643/16/14/2369.
