Antitumor activity of benzamide riboside and its combination with cisplatin and staurosporine

Benzamide riboside (BR), a new synthetic nucleoside analogue, has demonstrated a potent cytotoxic activity in murine leukemia in vitro. The purpose of the present investigation was to examine the antitumor activity of BR in mice bearing leukemia L1210. The results revealed that BR possesses a potent...

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Veröffentlicht in:European journal of pharmaceutical sciences 2001-02, Vol.12 (4), p.387-394
Hauptverfasser: Rauko, Peter, Novotny, Ladislav, Dovinova, Ima, Hunakova, Luba, Szekeres, Thomas, Jayaram, Hiremagalur N.
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container_end_page 394
container_issue 4
container_start_page 387
container_title European journal of pharmaceutical sciences
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creator Rauko, Peter
Novotny, Ladislav
Dovinova, Ima
Hunakova, Luba
Szekeres, Thomas
Jayaram, Hiremagalur N.
description Benzamide riboside (BR), a new synthetic nucleoside analogue, has demonstrated a potent cytotoxic activity in murine leukemia in vitro. The purpose of the present investigation was to examine the antitumor activity of BR in mice bearing leukemia L1210. The results revealed that BR possesses a potent antitumor activity in vivo. It increases life-span of mice with leukemia. Synergistic cytotoxicity of BR with select DNA damaging agents, cisplatin (cis-Pt) and staurosporine (STP) was examined in MTT chemosensitivity assay, FACS analyses and apoptotic DNA fragmentation on L1210 cells in culture. A simultaneous treatment of leukemia L1210 cells with the combination of BR and STP resulted in synergistic cytotoxicity that correlated with increased apoptotic activity in those cells. On the other hand, treatment of L1210 cells with combination of BR and cis-Pt resulted in antagonistic cytotoxic effect. Finally, to elucidate the synergistic effect of BR and STP in inducing apoptosis, the attention was directed to the activation of cell death processes through various cell cycle signals. This is the first report describing in vivo antitumor activity of BR and its utilization in combination chemotherapy.
doi_str_mv 10.1016/S0928-0987(00)00180-9
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The purpose of the present investigation was to examine the antitumor activity of BR in mice bearing leukemia L1210. The results revealed that BR possesses a potent antitumor activity in vivo. It increases life-span of mice with leukemia. Synergistic cytotoxicity of BR with select DNA damaging agents, cisplatin (cis-Pt) and staurosporine (STP) was examined in MTT chemosensitivity assay, FACS analyses and apoptotic DNA fragmentation on L1210 cells in culture. A simultaneous treatment of leukemia L1210 cells with the combination of BR and STP resulted in synergistic cytotoxicity that correlated with increased apoptotic activity in those cells. On the other hand, treatment of L1210 cells with combination of BR and cis-Pt resulted in antagonistic cytotoxic effect. Finally, to elucidate the synergistic effect of BR and STP in inducing apoptosis, the attention was directed to the activation of cell death processes through various cell cycle signals. 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subjects Animals
Antineoplastic agents
Antineoplastic Agents - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Apoptosis
Apoptosis - drug effects
Apoptosis - physiology
Benzamide riboside
Biological and medical sciences
Cisplatin
Cisplatin - administration & dosage
Cytotoxicity
Drug Screening Assays, Antitumor
Enzyme Inhibitors - administration & dosage
General aspects
Leukemia L1210 - drug therapy
Leukemia L1210 - mortality
Medical sciences
Mice
Mice, Inbred DBA
Murine leukemia cells
Nucleosides - administration & dosage
Pharmacology. Drug treatments
Staurosporine
Staurosporine - administration & dosage
Survival Rate
title Antitumor activity of benzamide riboside and its combination with cisplatin and staurosporine
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