Increased cyclooxygenase-2 and thromboxane synthase expression is implicated in diosgenin-induced megakaryocytic differentiation in human erythroleukemia cells.
Differentiation induction as a therapeutic strategy has, so far, the greatest impact in hematopoietic malignancies, most notably leukemia. Diosgenin is a very interesting natural product because, depending on the specific dose used, its biological effect is very different in HEL (human erythroleukemia) cells. For example, at 10 microM, diosgenin induced megakaryocytic differentiation, in contrast to 40 microM diosgenin, which induced apoptosis in HEL cells previously demonstrated using sedimentation field-flow fractionation (SdFFF). The goal of this work focused on the correlation between cyclooxygenase-2 (COX-2) and thromboxane synthase (TxS) and megakaryocytic differentiation induced by diosgenin in HEL cells. Furthermore, the technique of SdFFF, having been validated in our models, was used in this new study as an analytical tool that provided us with more or less enriched differentiated cell fractions that could then be used for further analyses of enzyme protein expression and activity for the first time. In our study, we showed the implication of COX-2 and TxS in diosgenin-induced megakaryocytic differentiation in HEL cells. Furthermore, we showed that the analytical technique of SdFFF may be used as a tool to confirm our results as a function of the degree of cell differentiation.
Laboratoire de Biochimie, EA 4021, Biomolécules et thérapies anti-tumorales, Faculté de Pharmacie, Institut GEIST, Université de Limoges, 87025 Limoges Cedex, France. bertrand.liagre@unilim.fr
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D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000819:agonists / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004144:Diosgenin / Q000494:pharmacology*; D031521:Fractionation, Field Flow; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects*; D008861:Microsomes / Q000378:metabolism; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism; D011003:Ploidies; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D052246:Cyclooxygenase 2 Inhibitors; D040201:Platelet Membrane Glycoprotein IIb; C016767:sulprostone; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D051546:Cyclooxygenase 2; D013930:Thromboxane-A Synthase; D004144:Diosgenin; D015232:Dinoprostone