Theophylline synergizes with chlorambucil in inducing apoptosis of B- chronic lymphocytic leukemia cells
| العنوان: | Theophylline synergizes with chlorambucil in inducing apoptosis of B- chronic lymphocytic leukemia cells |
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| المؤلفون: | Sylvie Baudet, Sandra Ktorza, F Mentz, Mossalayi, F Issaly, F Ouaaz, J. L. Binet, M Semichon, Hélène Merle-Béral |
| المصدر: | Blood. 88:2172-2182 |
| بيانات النشر: | American Society of Hematology, 1996. |
| سنة النشر: | 1996 |
| مصطلحات موضوعية: | medicine.medical_specialty, Programmed cell death, Chlorambucil, business.industry, Chronic lymphocytic leukemia, Immunology, Cell Biology, Hematology, Pharmacology, medicine.disease, Biochemistry, Leukemia, chemistry.chemical_compound, Endocrinology, chemistry, immune system diseases, Apoptosis, hemic and lymphatic diseases, Internal medicine, medicine, Cyclic adenosine monophosphate, Theophylline, Phosphodiesterase inhibitor, business, medicine.drug |
| الوصف: | We tested the effects of theophylline, a phosphodiesterase inhibitor inducing intracellular accumulation of cyclic adenosine monophosphate (cAMP), on malignant B cells from 15 patients with B-chronic lymphocytic leukemia (B-CLL). We observed a large increase in apoptotic cell numbers (mean, 90% v 20% in medium alone) in the presence of theophylline (100 micrograms/mL) or chlorambucil (10 mumol/L) after 72 hours of incubation. Maximal apoptosis (90%) was reached after 36 hours when the two drugs were used together at fourfold lower concentrations, indicating a synergistic effect; no effect was observed with normal B cells, suggesting that the combination might have therapeutic interest. Chlorambucil induced intracellular Ca+2 influx, pointing to the involvement of two signaling pathways that might explain its synergy with theophylline through their effects on oncogenes. The expression of bcl-2 protein, a proto-oncogene inhibiting apoptosis, decreased after incubation with the drugs, while c-myc, recently described as having a potent role in apoptosis, was overexpressed. For p53 we observed an overexpression in the presence of chlorambucil or both theophylline- chlorambucil and a decrease after theophylline incubation. Chlorambucil- and theophylline-induced apoptosis was partially inhibited by interleukin-4 (IL-4), which also abrogated the effects on oncogene expression. These results provide insight into the mechanisms underlying B-CLL apoptosis and suggest that the theophylline- chlorambucil combination may be of therapeutic value in this setting. |
| تدمد: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v88.6.2172.bloodjournal8862172 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::96846a78ed1a58ad76c5eaf0bf2d8518 https://doi.org/10.1182/blood.v88.6.2172.bloodjournal8862172 |
| رقم الانضمام: | edsair.doi...........96846a78ed1a58ad76c5eaf0bf2d8518 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
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| DOI: | 10.1182/blood.v88.6.2172.bloodjournal8862172 |