AUTHOR=Aryappalli Priyanka , Al-Qubaisi Sarah S. , Attoub Samir , George Junu A. , Arafat Kholoud , Ramadi Khalil B. , Mohamed Yassir A. , Al-Dhaheri Mezoon M. , Al-Sbiei Ashraf , Fernandez-Cabezudo Maria J. , al-Ramadi Basel K. TITLE=The IL-6/STAT3 Signaling Pathway Is an Early Target of Manuka Honey-Induced Suppression of Human Breast Cancer Cells JOURNAL=Frontiers in Oncology VOLUME=7 YEAR=2017 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2017.00167 DOI=10.3389/fonc.2017.00167 ISSN=2234-943X ABSTRACT=
There is renewed interest in the potential use of natural compounds in cancer therapy. Previously, we demonstrated the anti-tumor properties of manuka honey (MH) against several cancers. However, the underlying mechanism and molecular targets of this activity remain unknown. For this study, the early targets of MH and its modulatory effects on proliferation, invasiveness, and angiogenic potential were investigated using two human breast cancer cell lines, the triple-negative MDA-MB-231 cells and estrogen receptor-positive MCF-7 cells, and the non-neoplastic breast epithelial MCF-10A cell line. Exposure to MH at concentrations of 0.3–1.25% (w/v) induced a dose-dependent inhibition of the proliferation of MDA-MB-231 and MCF-7, but not MCF-10A, cells. This inhibition was independent of the sugar content of MH as a solution containing equivalent concentrations of its three major sugars failed to inhibit cell proliferation. At higher concentrations (>2.5%), MH was found to be generally deleterious to the growth of all three cell lines. MH induced apoptosis of MDA-MB-231 cells through activation of caspases 8, 9, 6, and 3/7 and this correlated with a loss of Bcl-2 and increased Bax protein expression in MH-treated cells. Incubation with MH induced a time-dependent translocation of cytochrome