Induction of apoptosis by 2-chloro-2'deoxyadenosine (2-CdA) alone and in combination with other cytotoxic drugs: synergistic effects on normal and neoplastic lymphocytes by addition of doxorubicin and mitoxantrone
| Autor: | Eckhart Weidmann, Hans Martin, Mathias J. Rummel, Petra Jantschke, Dieter Hoelzer, Paris S. Mitrou, Farsad Pourebrahim, Juergen Stein, Simone Boehrer, Simone Napieralski, Juergen Ries, Kai U Chow |
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| Rok vydání: | 2000 |
| Předmět: |
Cancer Research
2-Chloroadenosine Lymphoma Antineoplastic Agents Apoptosis Pharmacology In vivo medicine Tumor Cells Cultured Cytotoxic T cell Humans Doxorubicin Active metabolite Etoposide Mitoxantrone Deoxyadenosines Dose-Response Relationship Drug Chemistry Drug Synergism Hematology Dose–response relationship Oncology medicine.drug |
| Zdroj: | Leukemialymphoma. 36(5-6) |
| ISSN: | 1042-8194 |
| Popis: | 2-CdA is active as a single agent in the treatment of low-grade lymphomas. We analyzed the induction of apoptosis by 2-CdA alone (n=5) and in combination with other drugs in peripheral lymphocytes from 25 patients with leukemic low-grade lymphomas and from 25 healthy volunteers. 2-CdA was tested in 4 escalating concentrations (0.05 microg/ml to 0.4 microg/ml). Linear regressions showed a dose dependent apoptosis rate of 0.29 x microg 2-CdA/ml + 0.11 (r2=0.88, p=0.006) in normal cells and 0.41 x microg 2-CdA/ml + 0.15 (r2=0.88, p=0.005) in leukemic cells. Intracellular metabolization of 2-CdA into 2-CdA-5'mono-, -di- and the active metabolite -triphosphate was analyzed by HPLC and paralleled the dose dependent increase of apoptosis. The combination of 2-CdA with doxorubicin or mitoxantrone had a synergistic effect on the induction of apoptosis (p |
| Databáze: | OpenAIRE |
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