Honey bee venom combined with 1,25-dihydroxyvitamin D3 as a highly efficient inducer of differentiation in human acute myeloid leukemia cells

Purpose: Most cancer cells exhibit a defect in their capacity to mature into nonreplicating adult cells and existing in a highly proliferating state. Differentiation therapy by agents such as 1,25-dihydroxyvitamin D-3 (1,25-(OH)(2)VD3) represents a useful approach for the treatment of cancer including acute myeloid leukemia. Human myeloid leukemia cell lines are induced to terminal differentiation into monocyte lineage by 1,25-(OH)(2)VD3. However, usage of these findings in the clinical trials is limited by calcemic effects of 1,25-(OH)(2)VD3. Attempts to overcome this problem have focused on a combination of low concentrations 1,25-(OH)(2)VD3 with other compounds to induce differentiation of HL-60 cells. In this study, the effect of honey bee venom (BV) and 1,25-(OH)(2)VD3, individually and in combination, on proliferation and differentiation of human myeloid leukemia HL-60 cells were assayed. Materials and Methods: In this in vitro study, toxic and nontoxic concentrations of BV and 1,25-(OH)(2)VD3 were tested using Trypan blue stained cell counting and (3[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. In addition, differentiation of cells was assayed using a Wright-Giemsa staining and nitroblue tetrazolium reduction test. Data were analyzed by a one-way analysis of the variance test using SPSS software. Results: Our findings showed that both the BV and 1,25-(OH)(2)VD3, in a dose and time-dependent manner, caused cell death at high concentrations and inhibited cell proliferation at lower concentrations. About 5 nM of 1,25-(OH)(2)VD3 induced differentiation of HL-60 cells to monocytes after 72 h. 2.5 mu g/ml of BV suppressed proliferation of HL-60 cells but had not any effects on their differentiation, whereas in combination with 5 nM of 1,25-(OH)(2)VD3, it enhanced antiproliferative and differentiation potency of 1,25-(OH)(2)VD3. Conclusions: These results indicate that BV potentiates the 1,25-(OH)(2)VD3-induced HL-60 cell differentiation into monocytes