Synergistic induction of 1,25-dihydroxyvitamin D(3)- 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 anti-inflammatory 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 D(3) [1,25-(OH)(2) D(3)] 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)(2) D(3) 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)(2) D(3) or all- trans-RA in the differentiation therapy for myeloid leukemias. Abbreviations. 1,25-(OH)(2) D(3) :1,25-dihydroxyvitamin D(3) FITC:fluorescein isothiocyanate NBT:nitroblue tetrazolium RA:retinoic acid PE:phytoerythrin
Kim
Seung Hyun
SH
Immunology Laboratory, College of Pharmacy, Chonnam National University, Kwangju, Republic of Korea.
Kim
Tae Sung
TS
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D019306:Artemisia; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D008517:Phytotherapy; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D045787:Sesquiterpenes, Eudesmane; D014212:Tretinoin / Q000494:pharmacology
D000970:Antineoplastic Agents; D012717:Sesquiterpenes; D045787:Sesquiterpenes, Eudesmane; C117320:yomogin; D014212:Tretinoin; D019001:Nitric Oxide Synthase; D002117:Calcitriol