Sodium Selenite-Induced Apoptosis Mediated by ROS Attack in Human Osteosarcoma U2OS Cells

Abstract

Sodium selenite (Na(2)SeO(3), SSE) is an inorganic Se compound that is widely used in cancer chemoprevention studies. SSE has been shown to have anti-proliferative effects on several types of human cancer cells, but its effect on osteosarcoma cells has thus far not been reported. In this study, the cytotoxic effect of SSE on osteosarcoma cells U2OS was investigated in vitro and found to be higher than on comparable non-cancer cell lines 293 and L6. Treatment with SSE decreased cell growth in a dose- and time-dependent manner and altered cellular morphology. SSE also inhibited cell viability by inducing apoptosis, as evidenced by the formation of apoptotic bodies, generation of reactive oxygen species (ROS), and accumulation of cells during the advanced phase of apoptosis. SSE-induced apoptosis correlated with the activation of CASP 3, downregulation of BCL-2, and upregulation of P53 and PTEN in U2OS cells. These results indicated that SSE induces apoptosis in U2OS cells mainly through an ROS-mediated caspase pathway. This is the first report to show a possible mechanism of the anti-proliferative effect of SSE for the prevention of osteosarcoma in cell culture models.

In Vitro and in Vivo Mechanism of Bone Tumor Inhibition by Selenium-Doped Bone Mineral Nanoparticles

“…This is consistent with the earlier findings that ROS generation could induce osteosarcoma destruction. 34 …”

Substituted diaryl diselenides: Cytotoxic and apoptotic effect in human colon adenocarcinoma cells

“…It has been reported that selenium can inhibit cell proliferation, inducing injury via generation of reactive oxygen species (ROS) (Rudolf et al, 2008). ROS levels can activate the JNK pathway and caspases-3 and 9 via cytochrome c, with down-regulation of Bcl-2 and up-regulation of Bax (Chen et al, 2012). Also, it has been demonstrated that (C 6 H 5 Se) and (4-ClC 6 H 4 Se) 2 present higher thiol peroxidase activity and an improved antioxidant potential than (3-CF 3 C 6 H 4 Se) and (4-MeOC 6 H 4 Se) in vivo (Meotti et al, 2004).…”

“…c and DNA fragmentation. Other organic and inorganic selenium compounds have been shown to induce caspase-mediated apoptosis, including MeSeCys, selenite (Suzuki et al, 2010), sodium selenite (Chen et al, 2012), and selenium dioxide (SeO 2 ) (Rikiishi, 2007).…”

Herbal Remedy for Osteosarcoma - Challenging Evolution

“…SSE-triggered apoptosis correlated with the activation of CASP 3, downregulation of Bcl-2, and upregulation of P53, and PTEN in U2OS cells. Thus, the studies state that SSE is a promising anticancer compound that would be used in future therapies for OS [38].…”