ABSTRACT 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 VD 3 ) 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 VD 3 . However, usage of these findings in the clinical trials is limited by calcemic effects of 1,25‑(OH) 2 VD 3 . Attempts to overcome this problem have focused on a combination of low concentrations 1,25‑(OH) 2 VD 3 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 VD 3 , 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 VD 3 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 VD 3 , 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 VD 3 induced differentiation of HL‑60 cells to monocytes after 72 h. 2.5 μ 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 VD 3 , it enhanced antiproliferative and differentiation potency of 1,25‑(OH) 2 VD 3 . Conclusions: These results indicate that BV potentiates the 1,25‑(OH) 2 VD 3 ‑induced HL‑60
