Pro-apoptotic properties of hyperforin in leukemic cells from patients with B-cell chronic lymphocytic leukemia
| Autor: | J P Kolb, Fourneron Jd, Faussat Am, C Salanoubat, Claire Quiney, Naït-Si Y, Christian Billard, A. Ensaf |
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| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Programmed cell death Chronic lymphocytic leukemia Cell Blotting Western Nitric Oxide Synthase Type II Apoptosis Phloroglucinol Nitric Oxide chemistry.chemical_compound Bridged Bicyclo Compounds hemic and lymphatic diseases medicine Humans Caspase biology Terpenes Hematology Cell cycle medicine.disease Molecular biology Leukemia Lymphocytic Chronic B-Cell Hyperforin medicine.anatomical_structure Oncology chemistry Caspases Immunology biology.protein DNA fragmentation Cyclin-Dependent Kinase Inhibitor p27 |
| Zdroj: | Leukemia. 20(3) |
| ISSN: | 0887-6924 |
| Popis: | The effects of the hyperforin (HF), a natural phloroglucinol purified from Hypericum perforatum, were investigated ex vivo on leukemic cells from patients with B-cell chronic lymphocytic leukemia (B-CLL). HF was found to promote apoptosis of B-CLL cells, as shown by time- and dose-dependent stimulation of phosphatidylserine externalization and DNA fragmentation, by disruption of the mitochondrial transmembrane potential, caspase-3 activation and cleavage of the caspase substrate PARP-1. Moreover, HF-induced downregulation of Bcl-2 and Mcl-1, two antiapoptotic proteins that control mitochondrial permeability. HF also downregulated two proteins which are overexpressed by B-CLL patients' cells, the cell cycle inhibitor p27kip1 through caspase-dependent cleavage into a p23 form, and the nitric oxid (NO) synthase of type 2 (inducible NO synthase). This latter was accompanied by reduction in the production of NO known to be antiapoptotic in B-CLL cells. Preventing effects of the general caspase inhibitor z-VAD-fmk indicated that HF-promoted apoptosis of B-CLL cells was mostly caspase dependent. Furthermore, normal B lymphocytes purified from healthy donors appeared less sensitive to HF-induced apoptosis than B-CLL cells. These results indicate that HF may be of interest in the development of new therapies for B-CLL based on the induction of apoptosis and combination with cell cycle-dependent antitumor drugs. |
| Databáze: | OpenAIRE |
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