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

Benzamide riboside (BR), a new synthetic nucleoside analogue, has demonstra ted a potent cytotoxic activity in murine leukemia in vitro. The purpose of the present investigation was to examine the antitumor activity of BR in m ice 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, FAGS 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 c ells with combination of BR and cis-Pt resulted in antagonistic cytotoxic e ffect. Finally, to elucidate the synergistic effect of BR and STP in induci ng apoptosis, the attention was directed to the activation of cell death pr ocesses through various cell cycle signals. This is the first report descri bing in vivo antitumor activity of BR and its utilization in combination ch emotherapy. (C) 2001 Elsevier Science B.V. All rights reserved.