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 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.
Rauko
P
P
Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, SK-833 91 Bratislava, Slovak Republic.
Novotny
L
L
Dovinova
I
I
Hunakova
L
L
Szekeres
T
T
Jayaram
H N
HN
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002945:Cisplatin / Q000008:administration & dosage; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D007939:Leukemia L1210 / Q000188:drug therapy / Q000401:mortality; D051379:Mice; D008811:Mice, Inbred DBA; D009705:Nucleosides / Q000008:administration & dosage; D019311:Staurosporine / Q000008:administration & dosage; D015996:Survival Rate
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009705:Nucleosides; C076145:3-(1-deoxyribofuranosyl)benzamide; D019311:Staurosporine; D002945:Cisplatin