Size effects of realgar particles on apoptosis in a human umbilical vein endothelial cell line: ECV-304.

Regulation of endothelial cell apoptosis is a critical modulator of normal and pathological angiogenesis. Inorganic arsenic, especially arsenic trioxide, has been demonstrated to induce clinical remission in patients with acute promyelocytic leukemia as well as those with several solid cancers. So, in this study, we examined the in vitro effect of realgar(As2S2), used to treat human diseases for centuries in traditional Chinese medicine, on cell survival and apoptosis in a human umbilical vein endothelial cell (HUVEC) line: ECV-304. Four different suspensions of realgar particles with diameters from 100-500 nm containing equivalent doses were investigated to determine their size effects. After 2, 4, 6 and 8 h, realgar particles of diameters 100 nm and 150 nm obviously reduced ECV-304 cell survival, which was evidenced by a reduction of cell viability in the MTT assay, whereas cells exhibited slight viability reduction in response to treatment with realgar particles of diameters 200 nm and 500 nm. Significant apoptosis was identified by morphological observation, flow cytometry assay and DNA gel electrophoresis in the ECV-304 cells by the presence of realgar particles of diameters 100 nm and 150 nm. It is demonstrated that particles of realgar with average diameters from 100 nm to 150 nm can induce ECV-304 cell apoptosis. These results suggest that particles of realgar smaller than 150 nm may provide a less toxic agent for anti-neoplasia by suppressing angiogenesis. Copyright 2001 Academic Press.