Analysis of Selenium Levels in Osteosarcoma Patients and the Effects of Se-Methylselenocysteine on Osteosarcoma Cells In Vitro

Abstract

The form of selenium appears to be important for preventing cancer in humans. Here, we evaluated selenium levels in the serum and bone tissue samples from osteosarcoma patients using atomic absorption spectrometry. The in vitro effects of Se-methylselenocysteine (Se-MSC) on growth, cell cycle status, and apoptosis of osteosarcoma cells were assessed using the WST-1 assay, Hoechst 33342/propidium iodide staining, and flow cytometry, respectively. In osteosarcoma cases, the mean serum selenium levels in osteosarcoma tissue and normal bone were 0.08 mg/kg and 0.03 mg/kg, respectively (P < 0.05). Serum selenium levels in osteosarcoma and non-osteosarcoma cases were 0.09 mg/L and 0.08 mg/L, respectively (P > 0.05). Se-MSC-treated MG63 cells showed altered cellular morphology, decreased viability in a time- and dose-dependent manner, and an increase in the sub-G1 cell population. Se-MSC also downregulated Bcl-2 expression and upregulated Bax. Se-MSC inhibited the proliferation of the drug-resistant osteosarcoma cell line Saos-2/MTX300 and enhanced the inhibitory effect of pirarubicin on MG63 cells. Our data demonstrate that selenium levels are significantly higher in osteosarcoma tissue than normal bone tissue in osteosarcoma patients. The results also support the anticancer effects of Se-MSC in osteosarcoma. Further development of Se-MSC as an ancillary chemotherapy agent in osteosarcoma is warranted.

Emerging Anticancer Potentials of Selenium on Osteosarcoma

“…Inorganic and organic forms of selenium including SeO 2 [49], SeO 3 2− [50], selenium-polysaccharide (Se-Poly) [51], MSeA [52,53], Se-MSC [54] and SeC [55] induce cytotoxicity, anti-proliferation and apoptosis on osteosarcoma cells. These anticancer properties of inorganic and organic selenium were studied using mouse osteosarcoma K7M2 cells [56,57] and several human osteosarcoma cell lines, such as MG-63 [49,54,55,58,59,60], U-2 OS [49,50,51,52,53,61], Saos-2 [49,62], drug-resistant Saos-2/MTX300 [54], 143B [63,64,65] and MNNG/HOS cells [66]. SeO 3 2− concentration (as low as 10 µM) inhibits the 12−day colony formation activities of U-2 OS cells [50].…”

“…SeO 3 2− concentration (as low as 10 µM) inhibits the 12−day colony formation activities of U-2 OS cells [50]. Organic selenium, such as SeC and Se-MSC, also induces cell cycle arrest and sub-G1 accumulation in MG-63 cells [54,55]. SeC-induced S-phase arrest is associated with the downregulation of cyclinA and cyclin-dependent kinase-2 (CDK-2) proteins [55].…”

“…SeC-induced S-phase arrest is associated with the downregulation of cyclinA and cyclin-dependent kinase-2 (CDK-2) proteins [55]. Most of the cytotoxicity and anti-proliferation effects of selenium species are time-, concentration- or cell type-dependent [49,50,51,54,55]. For example, MSeA significantly increases the level of necrosis in U-2 OS cells within a longer treatment time period (48 h) [52].…”

“…For example, MSeA significantly increases the level of necrosis in U-2 OS cells within a longer treatment time period (48 h) [52]. Se-MSC inhibits the growth of MG-63 cells, but enhances that of U-2 OS cells in a concentration-independent manner [54]. This finding indicates that each selenium species may exert different effects on osteosarcoma cell models.…”

“…Various forms of selenium species, including SeO 2 [49], SeO 3 2− [50], Se-MSC [54] and SeC [55] induce apoptosis of human osteosarcoma cells by showing typical apoptotic morphological and ultrastructural changes. However, the molecular mechanism of selenium-induced cell death is poorly characterised.…”