Biological activity of acacia honey and its flavonoid on murine and human melanoma cells

Honey has been an ingredient of traditional medicine since ancient times due to a broad spectrum of therapeutic properties including antibacterial, cytostatic and antiinflammatory activity. The therapeutic properties of honey are acquiring importance for the treatment of acute and chronic free radical-mediate diseases such as atherosclerosis, diabetes and cancer. Honey is a concentrated aqueous solution of inverted sugars, it is reported to contain different substances including protein, minerals, both enzymatic and non-enzymatic antioxidants, including plant secondary metabolites. Flavonoids exhibit a wide range of biological effects, including the inhibition of reactive oxygen species generation and anticancer properties. In this work have been identified and quantified the secondary metabolites present in acacia honey and assessed its antioxidant activity. The results showed that acacia honey contained a good ammount of secondary metabolites and had a good antioxidant potential. Furthermore the results of HPLC analysis showed that chrysin was the principal compounds present in this type of honey. Our attention focuses on the possible role that acacia honey and chrysin may act as potential anticancer agents. Therefore, we tested their biological activity in murine and human melanoma cell lines (B16-F1 and A375). The results showed that both the tested compounds induced an antiproliferative effect on melanoma cells in a dose- and time-dependent manner. Flow cytometry analysis indicated that cytotoxicity induced by honey or chrysin was mediated by G0/G1 cell cycle arrest and induction of hyperploid progression. This study demonstrated also that chrysin induced cell differentiation in human and murine melanoma cells through synthesis, increase and intracellular accumulation of protoporphirin IX (PpIX) during treatment. Furthermore, following treatments with chrysin, an increase in the expression of porphobilinogen deaminase (PBG-D) was also noted. Finally, chrysin induces cell death through caspase-dependent mechanisms, involving down-regulation of ERK 1/2, activation of p38 MAPK and activation and translocation of Bax in mithocondrial fraction.