LAUSR

Natural products with bioactive components are widely studied on various cancer cell lines for their possible cytotoxic effects, recently. Among these products, honey stands out as a valuable bee product containing many active phenolic compounds and flavonoids. Numerous types of multifloral honey and honeydew honey are produced in Turkey owing to its abundant vegetation. Therefore, in this study, we investigated the cytotoxic effects of particular tree‐originated honeys from chestnut, cedar, pine, and multifloral honey on cell lines representing different types of the most common cancer of women, breast cancer, MCF7, SKBR3, and MDAMB‐231, and fibrocystic breast epithelial cell line, MCF10A as a control. All honey samples were analyzed biochemically. The dose‐ (1, 2.5, 5, 7.5, and 10 µg/mL) and time (24th, 48th, and 72nd hours)‐dependent effects of ethanol/water solutions of the honey samples were scrutinized. Cell viability/cytotoxicity was evaluated by the water soluble tetrazolium Salt‐1 (WST‐1) method. Apoptotic status was detected by Annexin V‐PI assay using FACSCalibur. The statistical analysis was performed using GraphPad Prism 6 and the clustering data analysis with the R programming language. The biochemical analyses of the honey samples showed that the tree‐originated honey samples contained more total phenolic compounds than the multifloral honey. Phenolic content of the honey types increases in order of multifloral, pine, cedar, and chestnut, respectively, which is compatible with their cytotoxic affectivity and dark color. In addition, the antioxidant capacity of the studied honey types was observed to increase in order of multifloral < pine < cedar ≅ chestnut. According to the WST‐1 data, chestnut honey induced cytotoxicity over 50% on all the cell lines, including the control MCF10A cells, even with low doses (honey concentrations starting from 1 µg/mL) (P < 0.0001). Similarly, Cedar honey was observed to be the second most effective honey in this study. Cedar honey, with the dose of 1 µg/mL, was detected statistically highly significant on MCF10A, MCF7, and SKBR3. In contrast, pine honey showed dramatically significant cytotoxicity only on the MDAMB 231 cells with a 1 µg/mL dose at the same time point (P = 0.018). While pine honey caused an anticancer effect on the MCF‐7 and SKBR3 cancer cell lines with a 2.5–5 µg/mL dose (P < 0.0001), like cedar and chestnut honeys, it increased the viability of the MCF10A control cells with the doses of 2.5–5 µg/mL. It only showed cytotoxicity with higher doses (10 µg/mL) on the MCF10A cell line (P < 0.0001). Moreover, we have observed that the multifloral and artificial honey samples were mostly ineffective or increased cell viability with the doses of 1–5 µg/mL. Apoptotic effects of the other honey samples on the MCF‐7 cell line were found as chestnut> pine> cedar> multifloral in the Annexin V‐propidium iodide (PI) analysis. Chestnut, cedar, and pine honey displayed a remarkably cytotoxic effect on breast cancer cell lines, MCF7, SKBR3, and even on the most aggressive MDAMB 231, representing the triple negative breast cancer, which lacks of targeted anticancer therapy. The chestnut and cedar honeys stand out to be the most cytotoxic on all cell lines, while pine honey was found to be the least toxic on control cells with appropriate toxicity on the cancer cells. © 2017 IUBMB Life, 69(9):677–688, 2017