Induction of megakaryocytic differentiation in chronic myelogenous leukemia cell K562 by 3-hydrogenkwadaphnin.
3-Hydrogenkwadaphnin (3-HK) is a daphnane-type diterpene ester isolated from Dendrostellera lessertii (Thymelaeaceae) with high differentiation and apoptotic potency in leukemic cells without any measurable adverse effects on normal cells (Moosavi et al., 2005b). In this study, we report that 3-HK (12 nM) has the ability to cease proliferation, induce differentiation and apoptosis in chronic myelogenous leukemia (CML) K562 cell line. The treated cells lost erythroid properties and differentiated along the megakaryocytic lineage based on the morphological features apparent after Wright-Giemsa staining, DNA content analysis and the expression of cell surface marker glycoprotein IIb as analyzed by flow cytometry. Moreover, using Hoechst 33258 and Annexin V double staining indicated the occurrence of apoptosis among the treated cells. On the other hand, restoration of the depleted GTP pool size by exogenous addition of guanosine (50 microM) reduced the effect of the drug regarding the extent of differentiation while no further enhancement of 3-HK effect was obtained by addition of exogenous hypoxanthine (100 microM). These interesting results necessitate further investigation regarding the mechanism of action of this unique anti-leukemic agent.
Meshkini
Azadeh
A
Institute of Biochemistry and Biophysics, P. O. Box 13145-1384, University of Tehran, Tehran, Iran.
Yazdanparast
Razieh
R
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006151:Guanosine / Q000494:pharmacology; D006801:Humans; D019271:Hypoxanthine / Q000494:pharmacology; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008533:Megakaryocytes / Q000187:drug effects* / Q000473:pathology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011123:Polyploidy; D034061:Thrombopoiesis / Q000187:drug effects
C505417:3-hydrogenkwadaphnin; D000970:Antineoplastic Agents; D004224:Diterpenes; D004791:Enzyme Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D006151:Guanosine; D019271:Hypoxanthine; D007168:IMP Dehydrogenase