Hydrogen bonding interactions between arsenious acid and dithiothreitol/dithioerythritol at different pH values: A computational study under explicit solvent model

Sulfhydryl compounds are regarded as potential functional monomers for arsenious acid imprinted polymers due to their high affinity to arsenious acid in aqueous solution. However, the recognition and binding mechanism...

Bortezomib Combined with Harringtonine or Arsenious Acid Induced Apoptosis in HL-60 Cells and Its Mechanism.

Objective: To explore the apoptosis effect induced by bortezomib combined with harringtonine or arsenious acid in HL60 cell line and the mechanism. Methods: Cell’s apoptosis was demonstrated by MTT assay and Hoechst33342 staining. Expression of Bcl-2, Caspase-9, Caspase-3 and PARP protein was detected by western blotting. Results: HL60 cells’ apoptosis could be induced by bortezomib, harringtonine and arsenious acid respectively, and the apoptosis effect was inhanced significantly when bortezomib combined with harringtonine or arsenious acid. Western blotting showed Bcl-2 protein was down-regulated and Caspase-9, Caspase-3 and PARP proteins were all cleaved activation when cells were treated by 15uM arsenious acid alone, but only cleaved activation of PARP and down-regulation of Bcl-2 protein be detected when cells were treated with 30nM harringtonine alone, expression of Caspase-9 and Caspase-3 has no change compared with the control. The changes of associated proteins were paralleled with the cell’s apoptosis when treated with combined drugs. Conclusion: HL60 cells’ apoptosis could be inhanced significantly when treated by bortezomib combined with harringtonine or arsenious acid compared with treated by bortezomib alone. Arsenious acid and bortezomib can inhibit caspase signaling pathway and down-regulate the expression of Bcl-2 protein together, but harringtonine and bortezomib can only down-regulate the expression of Bcl-2 protein and induce cleaved activation of PARP together.

Malevolent arsenic

We can never know who committed the first murder with arsenic or even who discovered the deadly nature of arsenical compounds. Although the natural arsenic minerals orpiment and realgar are poisonous, they are not particularly effective as murder weapons because they are insoluble and highly coloured, so that feeding them undetected to the intended victim would not be easy. The most reliable form in which to administer arsenic, knowing that it would succeed in killing someone, would have to be as the oxide. This is not a naturally occurring substance but it was easily obtained. When copper ores that had arsenic as an impurity were smelted, the arsenic was oxidized and emitted as white smoke, some of which sublimed (changed directly from a solid to a vapour) onto the walls of flues and chimneys of the smelter, from where it could be gathered. When people talk of ‘arsenic’ they are almost invariably referring to its oxide, whose chemical formula is As2O3, with arsenic atoms bonded to oxygen atoms. Over the centuries this has had many names such as white arsenic, arsenious oxide, arsenious acid (because it dissolves in water to form an acidic solution), arsenic trioxide, and its proper chemical name, arsenic(III) oxide. I shall call it by the name which is still in common use even among chemists: arsenic trioxide. Some murderers used solid arsenic trioxide, stirring it into foods like stews, porridge, or rice pudding to disguise it, but the more usual method was to dissolve it in something that the victim would drink. Not only is arsenic trioxide soluble, but the solution in which it is dissolved does not betray its presence because it is colourless and almost tasteless; if anything it imparts a slightly sweetish taste to the water. Yet even with such advantages favouring the would-be poisoner, it was still possible to fail to kill, either by not understanding arsenic trioxide’s simple chemistry or misjudging the dose required. Sometimes the ignorance and incompetence of murderers worked in their favour because repeated small doses of the poison gave the impression that the victim was suffering from some deep-seated illness, so that when a final fatal dose was administered the end was not unexpected.