Brain Neoplasms ; metabolism ; Cell Line, Tumor ; Glioma ; metabolism ; Humans ; Neoplastic Stem Cells ; drug effects ; metabolism ; Reactive Oxygen Species ; metabolism ; Sodium Selenite ; pharmacology

OBJECTIVE: Epidemiological studies suggest that selenium protects against the development of several cancers. Selenium (sodium selenite) has been reported to interfere with cell growth and proliferation, and to induce cell death. In this study, we tested whether selenium could have growth-inhibiting effect in ovarian cancer cells and an orthotopic animal model. METHODS: Cell growth in selenium-treated cells was determined in human ovarian cancer cells, A2780, HeyA8, and SKOV3ip1 using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Animal experiment of selenium with paclitaxel was performed using SKOV3ip1 cells in nude mice to evaluate their inhibiting effect for tumor growth. In addition, another animal experiment of paclitaxel with or without selenium was performed to assess the effect of survival and food intake in mice. RESULTS: The in vitro growth of selenium-treated cells was significantly decreased dose-dependently in A2780, HeyA8, and SKOV3ip1 cells. Therapy experiment in mice was started 1 week after injection of the SKOV3ip1 cells. Treatment with selenium (1.5 mg/kg, 3 times/week) and paclitaxel injection showed no addictive effect of the inhibition of tumor growth. However, combination of selenium and paclitaxel showed the slightly increased food intake compared with paclitaxel alone. CONCLUSION: Although selenium has growth-inhibiting effect in ovarian carcinoma cells in vitro, there is no additive effect on tumor growth in mice treated with combination of paclitaxel and selenium. However, food intake is slightly higher in selenium-treated mice during chemotherapy.
Animal Experimentation ; Animals ; Cell Death ; Cell Survival ; Eating ; Humans ; Mice ; Mice, Nude ; Ovarian Neoplasms ; Paclitaxel ; Selenium ; Sodium Selenite

Recent evidence has suggested that human skin fibroblasts may represent a novel source of therapeutic stem cells. In this study, we report a 3-stage method to induce the differentiation of skin fibroblasts into insulin-producing cells (IPCs). In stage 1, we establish the isolation, expansion and characterization of mesenchymal stem cells from human labia minora dermis-derived fibroblasts (hLMDFs) (stage 1: MSC expansion). hLMDFs express the typical mesenchymal stem cell marker proteins and can differentiate into adipocytes, osteoblasts, chondrocytes or muscle cells. In stage 2, DMEM/F12 serum-free medium with ITS mix (insulin, transferrin, and selenite) is used to induce differentiation of hLMDFs into endoderm-like cells, as determined by the expression of the endoderm markers Sox17, Foxa2, and PDX1 (stage 2: mesenchymal-endoderm transition). In stage 3, cells in the mesenchymal-endoderm transition stage are treated with nicotinamide in order to further differentiate into self-assembled, 3-dimensional islet cell-like clusters that express multiple genes related to pancreatic beta-cell development and function (stage 3: IPC). We also found that the transplantation of IPCs can normalize blood glucose levels and rescue glucose homeostasis in streptozotocin-induced diabetic mice. These results indicate that hLMDFs have the capacity to differentiate into functionally competent IPCs and represent a potential cell-based treatment for diabetes mellitus.
Animals ; Biological Markers/metabolism ; *Cell Culture Techniques ; *Cell Differentiation ; Cell Proliferation/drug effects ; Cell Separation ; Cells, Cultured ; Dermis/*cytology/drug effects ; Diabetes Mellitus, Experimental/*surgery ; Female ; Fibroblasts/*cytology/drug effects ; Genitalia, Female/*cytology ; Glucose/metabolism ; Hepatocyte Nuclear Factor 3-beta/metabolism ; Homeodomain Proteins/metabolism ; Humans ; Insulin/pharmacology/secretion ; Insulin-Secreting Cells/*cytology/metabolism ; *Islets of Langerhans Transplantation ; Mesenchymal Stem Cells/*cytology/drug effects/metabolism ; Mice ; Mice, Nude ; Niacinamide/pharmacology ; Recovery of Function ; SOXF Transcription Factors/metabolism ; Sodium Selenite/pharmacology ; Trans-Activators/metabolism ; Transferrin/pharmacology

OBJECTIVETo explore the effects of sodium selenite on the expressions of beta-catenin and cyclin D1 in colorectal cancer cells HCT 116 and SW480.

METHODSHCT 116 and SW480 cells were treated by 10 micromol/L sodium selenite at different time points. The expressions and transcription of beta-catenin and cyclin D1 were detected by Western blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR), respectively. Meanwhile, the impact of MG132 (a proteasome inhibitor) pretreatment on the expressions of beta-catenin and cyclin D1 was observed through Western blot analysis. The interaction between beta-catenin and T cell factor 4 (TCF4) after selenite treatment was evaluated using co-immunoprecipitation assay.

RESULTSSodium selenite inhibited the expression of beta-catenin and transcription of its target such as cyclin D1. MG132 pretreatment prevented the inhibition of beta-catenin signaling triggered by selenite in HCT 116 and SW480 cells. Furthermore, selenite treatment disrupted the interaction between beta-catenin and TCF4 in HCT 116 and SW480 cells.

CONCLUSIONSSodium selenite can lower the expression levels of beta-catenin and its target cyclin D1, during which the proteasome-mediated degradative pathway may be involved. The decreased interaction between beta-catenin and TCF4 due to sodium selenite may be also involved in the regulation of beta-catenin signaling.

Cell Line, Tumor ; Colorectal Neoplasms ; metabolism ; Cyclin D1 ; metabolism ; HCT116 Cells ; Humans ; Sodium Selenite ; pharmacology ; beta Catenin ; metabolism

OBJECTIVETo assess the curative effects of different drugs on liver cell damage of rats induced by acute nickel carbonyl poisoning.

METHODSIn present study 220 SD rats were divided into control group (10 rats), carbonyl nickel group (10 rats), 20 mg/kg methylprednisolone group (40 rats), 100 mg/kg DDC group (40 rats), 10 µmol/kg sodium selenite group (40 rats), 0.25 ml shenfuhuiyangtang group (40 rats) and 20 mg/kg methylprednisolone with 100 mg/kg DDC group (40 rats). All rats except for control group inhaled passively 250 mg/m(3) carbonyl nickel for 30 minutes. At 4h and 30h after exposure, the drugs were given intraperitoneally to the rats. On the 3rd and 7th days after exposure, the liver samples were taken from 10 rats each group. The DNA damage of liver cells was detected using comet assay, the ultrastructure changes in liver cells were examined under an electronmicroscope.

RESULTSCompared to carbonyl nickel group, the tail lengths of liver cells in 5 groups administrated at 4 h or 30 h and tested on the 3rd or 7th day after exposure decreased significantly (P < 0.05). Compared to the control group, the tail lengths of liver cells in sodium selenite and shenfuhuiyangtang groups administrated at 4h after exposure or sodium selenite, shenfuhuiyangtang and methylprednisolone with DDC groups administrated at 30h after exposure increased significantly (P < 0.05 or P < 0.01), when tested on the 3rd day after exposure. Except from methylprednisolone sub-group administrated at 4h and tested on the 7th day after exposure, the tail lengths of liver cells in other groups administrated at 4 h or 30 h and tested on the 7th day after exposure increased significantly (P < 0.05). Compared to carbonyl nickel group, the Olive moment of liver cells in 5 groups administrated at 4 h or 30 h tested on the 3rd or 7th day after exposure decreased significantly (P < 0.05 or P < 0.01). Compared to the control group, the Olive moment of liver cells in following groups (selenite and shenfuhuiyangtang groups administrated at 4 h or 30 h and tested on the 3rd or 7th day after exposure, DDC group administrated at 4 h or 30 h and tested on the 7th day after exposure, DDC group administrated at 30h and tested on the 3rd day after exposure, and methylprednisolone with DDC group administrated at 30 h and tested on the 7th day after exposure) increased significantly (P < 0.05 or P < 0.01). As compared with carbonyl nickel group, the ultrastructure observation indicated that the nucleus and other organelles of liver cells in methylprednisolone, DDC and methylprednisolone with DDC groups administrated at 4h and tested on the 3rd day were access to normal levels.

CONCLUSIONThe results of present study showed that methylprednisolone, DDC and methylprednisolone with DDC could improve obviously the repair of rat liver cell damage induced by acute carbonyl nickel poisoning, and the curative effects of early treatment were better than those of later treatment.

Animals ; Chemical and Drug Induced Liver Injury ; drug therapy ; pathology ; DNA Damage ; Drugs, Chinese Herbal ; therapeutic use ; Hepatocytes ; pathology ; Male ; Methylprednisolone ; therapeutic use ; Organometallic Compounds ; poisoning ; Rats ; Rats, Sprague-Dawley ; Sodium Selenite ; therapeutic use ; Zalcitabine ; therapeutic use

OBJECTIVE: To investigate the effects of complex decongestive physiotherapy (CDPT) with sodium selenite compared to the effects of CDPT without sodium selenite for the treatment of breast cancer-related lymphedema (BCRL). METHOD: Patients (n=40) who were diagnosed with BCRL were randomly assigned to the two groups: sodium selenite group or the non-sodium selenite group. In the sodium selenite group, sodium selenite was administered for 100 days concurrently with CDPT. In the non-sodium selenite group, only CDPT was administered. The main outcome measurements included limb circumference (proximal, distal and total) to indicate volume changes, the visual analogue scale (VAS) and the short form-36 version 2 questionnaire (SF-36) scores to evaluate the quality of life (QoL) pre-treatment, 100 days post-treatment and 130 days post-treatment for each patient. RESULTS: The sodium selenite group experienced volume reduction of 8.22% and 9.21%, at 100 and 130 days post-treatment, respectively. The non-sodium selenite group experienced 5.57% and 6.11% reduction in swelling at the same periods. Between the two groups, more significant volume reduction was observed in the affected distal limbs of patients assigned to the sodium selenite group compared to patients in the non-sodium group. However, the VAS and the SF-36 scores were not significantly different between the two groups. CONCLUSION: Sodium selenite therapy in combination with CDPT is effective in reducing the volume of upper limb in BCRL, and significantly reduce the volume of the affected distal upper limb compared to CDPT alone.
Breast ; Extremities ; Humans ; Lymphedema ; Quality of Life ; Surveys and Questionnaires ; Sodium ; Sodium Selenite ; Upper Extremity

OBJECTIVETo investigate the protective effects of selenium on rat hippocampal neurons against ischemia-reperfusion (IR) injury.

METHODSThirty-two rats were randomly divided into sham-operated group, IR group and selenium-treated group, and in the latter two groups, cerebral IR injury was induced by middle cerebral artery occlusion; Na2SeO3 treatment was administer in selenium-treated group. At 14 days after reperfusion, the brain tissues were harvested from the rats and hippocampal neuron injuries were observed by TUNEL and Methylene Blue staining. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and nerve growth factor (NGF) in the hippocampal tissues were measured by ELISA.

RESULTSCompared with IR group, the rats in selenium-treated group showed no significant increase in the expression of m-NGF (P>0.05), but pro-NGF expression was significantly increased (P<0.05) in the hippocampal tissue. Na2SeO3 treatment significantly inhibited the expressions of TNF-α and IL-1β and decreased the apoptosis of hippocampal neurons following cerebral IR injury (P<0.05).

CONCLUSIONSelenium produces antiapoptotic effect to protect the hippocampal neurons following cerebral IR injury possibly not by increasing the level of m-NGF but by decreasing the expressions of the inflammatory factors.

Animals ; Apoptosis ; Brain Ischemia ; metabolism ; pathology ; Hippocampus ; cytology ; metabolism ; pathology ; Interleukin-1beta ; metabolism ; Male ; Nerve Growth Factor ; metabolism ; Neurons ; drug effects ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism ; pathology ; Sodium Selenite ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism

PURPOSE: To compare the protective effects of saponin and non-saponin Sun-ginseng extract fractions in a selenite-induced rat cataract model. METHODS: A total of 101 Sprague-Dawley rat pups were divided into four groups by treatment: Sun-ginseng, saponin fraction, non-saponin fraction, and control. For induction of cataracts, sodium selenite 15 nmol/g was injected subcutaneously in 13 day-old rat pups. Sun-ginseng extract 100 microgram/g (Group I, Ginseng Science, Seoul, Korea), saponin fraction 100 microgram/g (Group II), non-saponin fraction 100 microgram/g (Group III), and phosphate buffered saline (Control group) were injected intraperitoneally every two days for a total of seven injections. The rats were sacrified and their lenses were dissected and photographed at day 7 and 14, and the cataracts were graded according to the ratio of the cataract area to the total lens area. The blind method was used for the evaluation of the cataract area. RESULTS: At day 14, cataract formation rates (CFR) were 33.3% in group I, 76.4% in group II, 41.2% in group III, and 77.7% in the control group. The mean cataract area (MCA) was 13.4+/-20.8% in group I, 14.4+/-11.7% in group II, 5.7+/-7.7% in group III, and 15.8+/-12.1% in the control group. Group III showed statistically significant results compared with those of control group (CFR p=0.001, MCA p=0.001). We observed significantly lower incidence and smaller mean cataract area in Group I and Group III at day 7 compared with the control group (Group I, CFR p=0.018; Group III, CFR p=0.032, MCA p=0.005). CONCLUSIONS: The protective effects of Sun-ginseng extract are caused by the components in the non-saponin fraction, not by those in the saponin fraction, in a selenite-induced cataract rat model.
Animals ; Cataract ; Incidence ; Panax ; Rats ; Saponins ; Sodium Selenite ; Solar System

PURPOSE: To evaluate antioxidative and preventive effects of sea tangle extract on selenite-induced cataract formation. METHODS: Eighty SD rat pups were randomized into 8 groups. Group 1 received no injection of reagent (normal); Group 2 to 8 received injection of selenite (15 micromol/Kg, s.c.) was injected. In group 2 (control) and group 3, normal saline (i.p.) and ascorbic acid (i.p.) was injected on days 3~31. In groups 4~8, sea tangle extract (i.p.) was injected at a concentration of 12.5, 25, 50, 100, 200 mg/kg, respectively. Development of cataract was assessed and photographed weekly under slit lamp. Rat lenses were analyzed for antioxidant enzymes, glutathione peroxidase (GPx), superoxide dismutase and malondialdehyde. Furthermore, an amino acid analysis of sea tangle extract was performed. RESULTS: Significant differences (p<0.05) were seen in cataract development in group 7. Dense nuclear cataracts developed in 8 of 10 of the control group (group 2); Group 4~8 developed nuclear cataract with proportion of 6/10, 3/10, 2/10, 1/10, and 6/10 rats. In sea tangle injected group, levels of GPx were higher than in the ascorbic acid and control groups. In particular, group 7, injected with 100 mg/kg of sea tangle extract, showed significantly high level of enzyme. Results of the amino acid analysis showed sea tangle includes glutamate-glycine-cysteine, major constituents of glutathione (GSH). CONCLUSIONS: The glutamate-glycine-cysteine in sea tangle is supposed to increase the level of lens GSH and this may contribute to lowering cataract development. This study strongly supports the activity of sea tangle as an endogenous antioxidant and anticataract agent.
Animals ; Antioxidants ; Ascorbic Acid ; Cataract ; Glutathione ; Glutathione Peroxidase ; Malondialdehyde ; Rats ; Sodium Selenite ; Superoxide Dismutase

OBJECTIVETo explore the mechanism and significance of cytochrome c oxidase subunit IV (COX IV) downregulation during apoptosis of NB4 cells induced by sodium selenite.

METHODSNB4 cells were treated with 20 micromol/L sodium selenite at different time points. COX IV protein and mRNA were detected by Western blot and RT-PCR, respectively. NB4 cells were pretreated with reactive oxygen species (ROS) scavenger before selenite exposure, and then COX IV protein expression and caspase-3 activation were detected by Western blot. NB4 cells were pretreated with caspase-3 inhibitor before selenite exposure, and then COX IV protein expression was detected by Western blot. NB4 cells were transiently transfected with vectors to interfere with the expression of COX IV, and then the apoptosis induced by selenite was analyzed by flow cytometry.

RESULTSSodium selenite induced evident downregulation of COX IV protein in NB4 cells, while its mRNA level was almost unchanged. ROS scavenger completely reversed selenite-induced COX IV downregulation and caspase-3 activation. Caspase-3 inhibitor partially reversed selenite-induced COX IV downregulation. Interference with COX IV expression dramatically enhanced selenite-induced apoptosis of NB4 cells.

CONCLUSIONSCOX IV is remarkably downregulated during selenite-induced apoptosis of NB4 cells. ROS mediates COX IV downregulation and caspase-3 activation, while caspase-3 is partially involved in COX IV downregulation. COX IV interference markedly increases the sensitivity of NB4 cells to selenite-induced apoptosis.

Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Down-Regulation ; drug effects ; Electron Transport Complex IV ; genetics ; metabolism ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; RNA, Messenger ; genetics ; Reactive Oxygen Species ; metabolism ; Sodium Selenite ; pharmacology