A new synthetic drug, benzamide riboside (BR) exhibited strong oncolytic activity against leukemic cells in the 5-10 μM range. Higher BR-concentrations (20 μM) predominantly induced necrosis which correlated with DNA strand breaks and subsequent depletion of ATP- and dATP levels. Replenishment of the ATP pool by addition of adenosine prevented necrosis and favoured apoptosis. This effect was not a pecularity of BR-treatment, but was reproduced with high concentrations of all trans-retinoic acid (120 μM) and cyanide (20 mM). Glucose was also capable to suppress necrosis and to favour apoptosis of HL-60 cells, which had been treated with necrotic doses of BR and cyanide. Apoptosis eliminates unwanted cells without affecting the microenvironment, whereas necrosis causes severe inflammation of surrounding tissues due to spillage of cell fluids into the peri-cellular space. Thus, the monitoring and maintenance of cellular energy pools during therapeutic drug treatment may help to minimize nonspecific side effects and to improve attempted drug effects.
Bibliographical noteFunding Information:
We wish to thank Anton Jäger for his excellent technical assistance in preparing the figures. Grant support: This work was supported in part by the Herzfelder'sche Familienstiftung, the AICR-grant No. 97-12, the Anton Dreher Memorial Foundation to G Krupitza and by Austrian National Bank Fonds No. 8260 and the Hochschuljubiläumsfonds to T Szekeres.
- Benzamide riboside