Xanthohumol kills B-chronic lymphocytic leukemia cells by an apoptotic mechanism
| Autor: | A Janssens, Marc Bracke, Fritz Offner, Barbara Vanhoecke, Jan Philippé, Sofie Lust |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Programmed cell death Apoptosis Biology p38 Mitogen-Activated Protein Kinases Flow cytometry chemistry.chemical_compound Annexin Tumor Cells Cultured medicine Humans Phosphorylation Extracellular Signal-Regulated MAP Kinases Aged Flavonoids B-Lymphocytes Propiophenones Dose-Response Relationship Drug medicine.diagnostic_test Ribosomal Protein S6 Kinases 70-kDa Middle Aged Flow Cytometry medicine.disease Leukemia Lymphocytic Chronic B-Cell In vitro Leukemia chemistry Immunology Xanthohumol Cancer research Female Poly(ADP-ribose) Polymerases Signal transduction Food Science Biotechnology |
| Zdroj: | Molecular Nutrition & Food Research. 49:844-850 |
| ISSN: | 1613-4133 1613-4125 |
| DOI: | 10.1002/mnfr.200500045 |
| Popis: | B-chronic lymphocytic leukemia (B-CLL) is an indolent lymphoid malignancy with variable prognosis. Adverse prognostic factors comprise treatment resistance, cytogenetics (11q- and 17p-), the presence of unmutated Ig genes, and the more comprehensive activation marker Zap 70. In contrast to diminished sensitivity to chemotherapy, Zap 70+ B-CLL cells retain their responsiveness to manipulation of signal transduction and monoclonals. Xanthohumol (XA) has recently been documented to have an impact on breast cancer cell growth and invasiveness in vitro. Based on these observations, lymphocytes from patients with B-CLL were cultured in the presence of XA in vitro. XA induced a dose-dependent killing of B-CLL cells at an LD(50) ((24 h)) of 24.4 +/- 6.6 microM, independent of known adverse prognostic factors including functional loss of p53. Cell death was associated with poly (ADP)-ribose polymerase cleavage and annexin V positivity, suggestive of an apoptotic mechanism. Surprisingly, p 70(S 6 K) phosphorylation was stimulated upon XA treatment. In conclusion, XA has an antitumor activity on B-CLL cells in vitro. The molecular mechanisms behind this pro-apoptotic effect deserve further investigation. |
| Databáze: | OpenAIRE |
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