Maintenance of ATP favours apoptosis over necrosis triggered by benzamide riboside

Abstract

A new synthetic drug, benzamide riboside (BR) exhibited strong oncolytic activity against leukemic cells in the 5 ± 10 mM range. Higher BR-concentrations (20 mM) 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 mM) 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.

Subcellular localisation of Cdc25A determines cell fate

“…The surviving cells were trypsinised and pooled with supernatant cells and stained with Hoechst 33258/propidium iodide (HO/PI; Hoechst: final concentration 5 mg/ml and PI: final concentration 2 mg/ml) to monitor nuclear chromatin condensation, using a 4 0 -6-diamino-2-phenylindol (DAPI) filter in connection with a Zeiss Axiovert microscope. [42][43][44] Apoptosis of rat 423 cells, which was induced by serum withdrawal (7500 nM 4-OHT), was measured as described. 18 Expression, in vitro phosphorylation of GST-FKHRL1 and conjugation to glutathione-sepharose…”

Tuberin activates the proapoptotic molecule BAD

“…After an incubation period of 1 h at 371C, the cells were transferred onto glass slides and microscopically analysed with a DAPI filter. Viable and apoptotic cells were discerned and counted (Grusch et al, 2002).…”

Characterization of apoptosis-induced Mcm3 and Cdc6 cleavage reveals a proapoptotic effect for one Mcm3 fragment

“…Halting of ATP-consuming processes like DNA replication could therefore further the efficiency of apoptosis. 4 Indeed, cleavage of replication proteins by caspases, the executioner proteases for apoptosis, has been reported. 5 Here we show in detail the cleavage of the pre-RC proteins Mcm3 and Cdc6 by caspase-3 and caspase-7, including characterization of the cleavage sites.…”