Synergistic induction of 1,25,-dihydroxyvitamin D₃-and all-trans-retinoic acid-induced differentiation of HL-60 leukemia cells by yomogin, a sesquiterpene lactone from Artemisia princeps

Many anti-inflammatory agents are known to significantly enhance the terminal differentiation of some cancer cells such as leukemia cells. In this study, the effect of yomogin, a eudesmane sesquiterpene lactone isolated from Artemisia princeps with antiinflammatory activity, was investigated in human promyelocytic leukemia HL-60 cells. Yomogin by itself induced small increases in cell differentiation, with less than 19% of the cells attaining a differentiated phenotype. Importantly, yomogin synergistically enhanced differentiation of HL-60 cells in a dose-dependent manner when combined with either 5 nM 1,25-dihydroxyvitamin D₃ [1,25-(OH)₂D₃] or 50 nM all-trans retinoic acid (all-trans RA). Cytofluorometric analysis and morphologic studies indicated that the combinations of yomogin and 1,25-(OH)₂D₃ stimulated differentiation to monocytes whereas the combinations of yomogin and all-trans RA stimulated differentiation to granulocytes. These results suggest that yomogin may be useful in combination with 1,25-(OH)₂D₃ or all-trans-RA in the differentiation therapy for myeloid leukemias.