ENHANCEMENT OF 1,25-DIHYDROXYVITAMIN D3- AND ALL-TRANS RETINOIC ACID-INDUCED DIFFERENTIATION OF HUMAN LEUKEMIA HL-60 CELLS BY BLOOD SHELL, SCAPHARCA BROUGHTONII

Abstract

Human myeloid leukemia HL-60 cells are differentiated into monocytic or granulocytic lineage when treated with 1,25-dihydroxyvitamin D3 (1,25-[OH]2D3) or all-trans retinoic acid (RA), respectively. In this study, the effect of ethanol fraction prepared from the blood shell, Scapharca broughtonii, on cell differentiation was investigated in an HL-60 cell culture system. Treatment of HL-60 cells with 2.5- to 20-µg/mL ethanol fraction of the blood shell for 72 h inhibited cell proliferation and induced a 20% increase in cell differentiation, as demonstrated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium and nitroblue tetrazolium reduction assay. Interestingly, synergistic induction of HL-60 cell differentiation was observed when the ethanol fraction of the blood shell was combined with either 5-nM 1,25-(OH)2D3 or 50-nM all-trans RA. Flow cytometric analysis and morphologic studies confirmed that combinations of either 1,25-(OH)2D3 or all-trans RA and the ethanol fraction of the blood ark shell stimulated leukemia cell differentiation. These results suggest a possibility of blood shell in the treatment of human leukemia. PRACTICAL APPLICATIONS The ethanol fraction (SIII) of blood shell, Scapharca broughtonii, potentiates 1,25-(OH)2D3- and all-trans retinoic acid (RA)-induced differentiation in HL-60 myeloid leukemia cells. HL-60 cells might be synergistically differentiated into monocytes or granulocytes when treated with the ethanol fraction in combination with either 1,25-(OH)2D3 or all-trans RA. These results imply a possible application of blood ark shell in the treatment of leukemia patients with less toxicity.