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.

Abstract

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

• Authors: Seung Hyun Kim, Tae Sung Kim
• Journal: Planta medica (Planta Med) Vol. 68 Issue 10 Pg. 886-90 (Oct 2002) ISSN: 0032-0943 [Print] Germany
• PMID: 12391550 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Sesquiterpenes
• Sesquiterpenes, Eudesmane
• yomogin
• Tretinoin
• Nitric Oxide Synthase
• Calcitriol

Topics

• Antineoplastic Agents (administration & dosage, pharmacology, therapeutic use)
• Artemisia
• Calcitriol (pharmacology)
• Cell Differentiation (drug effects)
• Dose-Response Relationship, Drug
• Drug Synergism
• Drug Therapy, Combination
• Flow Cytometry
• Fluorescent Antibody Technique
• HL-60 Cells (drug effects)
• Humans
• Leukemia, Promyelocytic, Acute (drug therapy)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Phytotherapy
• Sesquiterpenes (administration & dosage, pharmacology, therapeutic use)
• Sesquiterpenes, Eudesmane
• Tretinoin (pharmacology)