Membrane toxicity accounts for apoptosis induced by realgar nanoparticles in promyelocytic leukemia HL-60 cells

Previous studies have demonstrated that realgar nanoparticles might provide a less toxic agent for antineoplasia by suppressing angiogenesis. Here, we addressed the question of whether the size effects on apoptosis induction mainly contribute to the comparably higher concentration of easily soluble As₂O₃ present in realgar nanoparticles. Results revealed that treatment with realgar nanoparticles resulted in considerably low cell viability and produced characteristic apoptotic events in HL-60 cells, including morphological changes, DNA ladder formation, and increased number of cells with sub-G1-phase, whereas raw realgar particles with the same As₂O₃ concentration failed to induce apoptosis. On the other hand, the effects of realgar nanoparticles and raw realgar particles on cell membrane were examined. Realgar nanoparticles had acute toxicity to cell membrane, potentiating lipid peroxidation, increasing lactate dehydrogenase (LDH) release, and reducing membrane fluidity, whereas raw realgar particles had little effect on cell membrane besides a similar reduction of membrane fluidity. These results suggest that the promotion of lipid peroxidation and membrane permeability might play an important role in the process of apoptotic induction by realgar nanoparticles. However, raw realgar particles are not sufficient to elicit apoptosis, although they can reduce membrane fluidity in HL-60 cells.