Strawberry tree honey as a new potential functional food. Part 1: Strawberry tree honey reduces colon cancer cell proliferation and colony formation ability, inhibits cell cycle and promotes apoptosis by regulating EGFR and MAPKs signaling pathways

The aim of this work was to assess the phytochemical composition and anticancer effects of Strawberry-tree honey (STH) on cellular proliferation, cell cycle and apoptosis in human colon adenocarcinoma (HCT-116) and metastatic (LoVo) cancer cells. Kaempferol and gallic acid were the major phenolic compounds. STH showed higher cytotoxic and anti-colonogenic effects in a time- and dose-dependent manner; it arrested cell cycle in S and G2/M and regulated cell cycle genes, such as cyclin D1, cyclin E, CDK2, CDK4, p21Cip, p27Kip and p-RB. STH treatment promoted apoptosis by modulating key genes (p53, caspase-3, c-PARP) as well as intrinsic (Bax/Bcl2, Cyto C and caspase-9) and extrinsic (Fas L and caspase-8) apoptotic factors. STH also caused endoplasmic reticulum stress by increasing ATF-6 and XBP-1 expressions, suppressed EGFR, HER2 and downstream markers (p-Akt and p-mTOR) and elevated p-p38MAPK and p-ERK1/2. In conclusion, STH have shown a chemo-preventive action on different colon cancer cell models.