Enhancement of 1,25-Dihydroxyvitamin D3- and All-trans Retinoic Acid-Induced HL-60 Leukemia Cell Differentiation by Panax ginseng

Ginseng (Panax ginseng C.A. Meyer) has a wide range of therapeutic uses including cancer treatment. Human promyelocytic leukemia cells differentiate into monocytes or granulocytes when treated with 1,25-dihydroxyvitamin D 3 [1,25-(OH) 2 D 3 ] or all-trans retinoic acid (ATRA). Treatment of HL-60 cells with zero to 100 μg/ml of a methanol extract of ginseng for 72 h induced a small increase in cell differentiation. Surprisingly, a synergistic induction of differentiation was observed when HL-60 cells were treated with ATRA or 1,25-(OH) 2 D 3 and the extract. The inhibitors of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK), but not of phosphoinositide 3-kinase (PI3-K), inhibited the HL-60 differentiation induced by the extract in combination with ATRA or 1,25-(OH) 2 D 3 , signifying that PKC and ERK were involved in the cell differentiation enhancement by the extract. These results suggest that the ability of a methanol extract of ginseng to enhance the differentiation potential of ATRA or 1,25-(OH) 2 D 3 may improve the ultimate outcome of acute promyelocytic leukemia therapy.