Triptolide cooperates with chemotherapy to induce apoptosis in acute myeloid leukemia cells
| Autor: | Francois-Xavier Mahon, Marie Jeanneteau, Josy Reiffers, Francis Lacombe, Maialene Uhalde, Arnaud Pigneux, Francis Belloc, Noel Milpied |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Myeloid Apoptosis X-Linked Inhibitor of Apoptosis Protein Biology Flow cytometry chemistry.chemical_compound Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols Genetics medicine Idarubicin Humans Annexin A5 Molecular Biology medicine.diagnostic_test Dose-Response Relationship Drug Cytarabine Myeloid leukemia Drug Synergism Cell Biology Hematology Cell cycle Triptolide Phenanthrenes medicine.disease carbohydrates (lipids) Leukemia Leukemia Myeloid Acute medicine.anatomical_structure chemistry Immunology Cancer research Epoxy Compounds Leukocyte Common Antigens I-kappa B Proteins Diterpenes Drug Screening Assays Antitumor medicine.drug |
| Zdroj: | Experimental hematology. 36(12) |
| ISSN: | 0301-472X |
| Popis: | Triptolide has shown antitumor activity in a broad range of solid tumors and on leukemic cells in vitro.The THP1 cell line and primary acute myeloid leukemia (AML) cells were cultured with triptolide alone or in association with AraC or idarubicin in increasing concentrations. Apoptosis was measured by flow cytometry using DiOC6(3) for the cell line and fluorescein isothiocyanateAnnexin-V and CD45 labeling for fresh blast cells. Protein expression was measured by Western blot. Cell cycle distribution of apoptotic cells was measured by flow cytometry.A synergistic effect was observed when triptolide was added to idarubicin or to AraC to induce apoptosis of THP-1 leukemic cells. The triptolide/AraC association was also investigated in vitro on primary blast cells from 25 AML patients. This combination induced significantly higher percentages of apoptosis vs treatment with each drug separately (p0.005). The IkappaB and X-linked inhibitor of apoptosis protein contents, which were altered by triptolide in idarubicin-treated cells, were not modified in AraC-treated cells. The association of AraC with triptolide increased the number of cells blocked in the S phase and most underwent apoptosis.These results suggest that, by modifying the cell cycle kinetics, AraC sensitizes AML cells to apoptosis induced by low concentration triptolide. The in vitro proapoptotic effect of triptolide associated with the antiproliferative activity of AraC warrants further clinical investigation for treatment of AML patients, especially elderly patients for whom low-dose AraC treatment could be improved by the addition of triptolide. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect