Inhibition of invasion and induction of apoptosis by selenium in human malignant brain tumour cells in vitro
Affiliations: Biomedical Sciences, School of Health and Social Sciences, Middlesex University, Queensway, Enfield, Middlesex, EN3 4SA, UK. firstname.lastname@example.org
- Published online on: May 1, 2007 https://doi.org/10.3892/ijo.30.5.1263
- Pages: 1263-1271
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Selenium is considered to be one of the most promising micronutrients for cancer prevention and therapy, based on evidence from epidemiological studies, laboratory-based research and clinical trial intervention. There are ample reports of selenium methionine and sodium selenite's ability to induce apoptosis in various cancers in vitro. There are a few reports in the literature on the effects of selenium on established glioma cell lines but none on biopsy-derived short-term brain tumour cultures. In this in vitro study the effects of a range of concentrations (2-10 µg/ml) of sodium selenite were investigated in one low-passage culture of biopsy-derived glioma cells (IPSB-18, an anaplastic astrocytoma, P 18-22) and a normal human brain cell culture (CC2565, P11). Results from 2 viability assays, 3[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and sulphorodamine B (SRB) consistently showed that the IC50 for selenium in the astrocytoma was approximately 5 µg/ml whilst the normal brain cells were unaffected by selenium in the range of concentrations studied. Time-lapse video microscopy revealed that, while at 4 µg/ml selenium, the time taken to achieve 100% cell death was 17 h, with increasing concentrations of selenium from 6 to 8 µg/ml and finally at 10 µg/ml the IPSB-18 cells rounded up and died much more quickly. The time taken to achieve 100% cell death was 7 h, 7 h and 6 h, respectively, suggesting that the effect was similar at higher concentrations. Flow cytometry indicated that cell death was by apoptosis. RT-PCR results showed downregulation of the gene expression of 6 matrix metalloproteases (MMP2, 9, 14, 15, 16, 24), their inhibitors, TIMPs and epidermal growth factor receptor, in IPSB-18 cells treated with 2, 4 and 8 µg/ml of selenium. Collectively, the data in this study suggests that selenium, not only induces tumour cell-specific apoptosis but also has anti-invasive potential.