Effects of realgar (tetra-arsenic tetra-sulfide) on malignant tumor cells.

e13525 Background: Realgar, of which the main component is tetra-arsenic tetra-sulfide, has been widely used in Chinese traditional medicine. Its therapeutic effects in traditional remedies include anti-inflammation, antiulcer, anticonvulsion, and anti-schistosomiasis, etc. It can be taken orally and has much less toxicity than arsenic trioxide, another arsenic compound applied to treat malignant diseases. Recent studies indicated beneficial effects of Realgar in the treatment of hematological malignant diseases. However, its effect on solid malignant tumor was unclear. This study was aimed to investigate the effect of Realgar on some solid malignant tumor cells. Methods: Four human solid malignant tumor cell lines, MKN45 cells (gastric cancer), A375 cells (malignant melanoma), Patu8988 cells (pancreatic carcinoma) and HepG2 cells (hepatocellular carcinoma) were treated with Realgar in vitro. Cell morphology was observed under microscope. Cell proliferation and cell cycle distribution were determined using methyl thiazollyl tetrazolium assay and flow cytometry respectively. Caspases activity was measured by colorimetric assay. Nuclear translocation of NF-κB was examined by western blot. For in vivo study, tumor implanted mice were treated with Realgar. Upon sacrifice, tumor weight was recorded. IL-2, IFN-γ and TNFα in the circulation were measured by ELISA. Results: Realgar had a dose-dependent cytotoxic effect on those malignant cells. However, only a minor effect on normal human cells (L02 embryonic liver cell) was observed with a similar concentration of Realgar. Further, Realgar-treated MKN45 cells and A375 cells showed a hypodiploid peak by flow cytometry. This change was accompanied by aberrant-regulation of NF-κB nuclear translocation and up-regulation of caspase-3 and caspase-9 activities, indicating mitochondrial pathway mediated cell apoptosis. Moreover, in implanted mice the tumor weight decreased after Realgar administration. In additional, TNFα decreased while IL-2 increased. Conclusions: Realgar displayed a significant anticancer effect on malignant cells through induction of cell apoptosis. Our findings suggested a potential therapeutic effect of Realgar on some solid malignant tumors.