Inhibition of invasion and induction of apoptosis by selenium in human malignant brain tumour cells in vitro.
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 microg/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 microg/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 microg/ml selenium, the time taken to achieve 100% cell death was 17 h, with increasing concentrations of selenium from 6 to 8 microg/ml and finally at 10 microg/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 microg/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.
Rooprai
Harcharan K
HK
Biomedical Sciences, School of Health and Social Sciences, Middlesex University, Queensway, Enfield, Middlesex, UK. b.rooprai@mdx.ac.uk
Kyriazis
Ioannis
I
Nuttall
Robert K
RK
Edwards
Dylan R
DR
Zicha
Daniel
D
Aubyn
Deborah
D
Davies
Derek
D
Gullan
Richard
R
Pilkington
Geoffrey J
GJ
D000293:Adolescent; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001254:Astrocytoma / Q000188:drug therapy* / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D008297:Male; D009361:Neoplasm Invasiveness; D012313:RNA / Q000378:metabolism; D012643:Selenium / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D000970:Antineoplastic Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D012313:RNA; C022616:thiazolyl blue; D012643:Selenium