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- Title
Manuka Honey Inhibits Human Breast Cancer Progression in Preclinical Models.
- Authors
Márquez-Garbán, Diana C.; Yanes, Cristian D.; Llarena, Gabriela; Elashoff, David; Hamilton, Nalo; Hardy, Mary; Wadehra, Madhuri; McCloskey, Susan A.; Pietras, Richard J.
- Abstract
Manuka honey (MH) exhibits potential antitumor activity in preclinical models of a number of human cancers. Treatment in vitro with MH at concentrations ranging from 0.3 to 5.0% (w/v) led to significant dose-dependent inhibition of proliferation of human breast cancer MCF-7 cells, but anti-proliferative effects of MH were less pronounced in MDA-MB-231 breast cancer cells. Effects of MH were also tested on non-malignant human mammary epithelial cells (HMECs) at 2.5% w/v, and it was found that MH reduced the proliferation of MCF-7 cells but not that of HMECs. Notably, the antitumor activity of MH was in the range of that exerted by treatment of MCF-7 cells with the antiestrogen tamoxifen. Further, MH treatment stimulated apoptosis of MCF-7 cells in vitro, with most cells exhibiting acute and significant levels of apoptosis that correlated with PARP activation. Additionally, the effects of MH induced the activation of AMPK and inhibition of AKT/mTOR downstream signaling. Treatment of MCF7 cells with increased concentrations of MH induced AMPK phosphorylation in a dose-dependent manner that was accompanied by inhibition of phosphorylation of AKT and mTOR downstream effector protein S6. In addition, MH reduced phosphorylated STAT3 levels in vitro, which may correlate with MH and AMPK-mediated anti-inflammatory properties. Further, in vivo, MH administered alone significantly inhibited the growth of established MCF-7 tumors in nude mice by 84%, resulting in an observable reduction in tumor volume. Our findings highlight the need for further research into the use of natural compounds, such as MH, for antitumor efficacy and potential chemoprevention and investigation of molecular pathways underlying these actions.
- Subjects
THERAPEUTIC use of honey; EPITHELIAL cells; IN vitro studies; CHEMOPREVENTION; BIOLOGICAL models; PHOSPHORYLATION; RESEARCH funding; PROTEIN kinases; BREAST tumors; ANTINEOPLASTIC agents; CELL proliferation; APOPTOSIS; TREATMENT effectiveness; DESCRIPTIVE statistics; TAMOXIFEN; CELLULAR signal transduction; IN vivo studies; XENOGRAFTS; PLANT extracts; CELL lines; MICE; ANIMAL experimentation; MTOR inhibitors; STAT proteins; DISEASE progression; PHARMACODYNAMICS
- Publication
Nutrients, 2024, Vol 16, Issue 14, p2369
- ISSN
2072-6643
- Publication type
Article
- DOI
10.3390/nu16142369