Possible Interaction: Glutathione and Arsenic Trioxide

“Treatment of leukemic cells with ATO , PRT and BSO rapidly depleted cells from glutathione , induced oxidative stress and decreased intracellular ATP levels.”

“Therefore, our study suggests that strategies to inhibit the compensatory increase of glutathione and block the interaction between leukemic cells and BM stromal cells should be employed before applying ATO to non-APL hematologic malignancies.”

“Although ATO transiently increased GSH levels at 5 min, Trx1 and TrxR1 siRNAs reduced the increased GSH levels in these cells.”

“Our data demonstrated that NaAsO2 and As2O3 disrupted the balance of GSH homeostasis, and NaAsO2- and As2O3-induced oxidative damage was closely associated with the imbalance in GSH synthesis, recycling and utilization.”

“First, with the combination of arsenic … effect and cytotoxicity decrease when glutathione concentration increases; second, arsenic methylation, stable arsenic methylation products weaken the apoptosis effect of arsenic trioxide in leukemia … affect the sensitivity of tumor cells to arsenic trioxide and increase the resistance of leukemia cells to arsenic trioxide.”

“Furthermore, low concentrations of ATO and realgar nanoparticles increased the content of intracellular glutathione and elevated γ-H2AX expression confirmed DNA damage preferentially at higher concentrations of both drugs used.”

“Also, our experimental results showed that intracellular glutathione (GSH) contents were increased by various doses of BaP, but single or cotreatment with As2O3 significantly decreased the GSH level in the cells at all tested concentrations.”

“ ATO increased ROS levels including O2•- and GSH depleted cell numbers.”

“ ATO induced cell growth inhibition and death in HPF cells and it increased ROS levels including O2•- and GSH depleted cell number.”

“Taken together, these results indicate that GSH depleting agents or pro-oxidative chemicals have capabilities of improving the utility of As2O3 in ovarian cancer management.”