A simple and convenient procedure for stereoselective synthesis of (Z)-allyl selenides has been developed by a one-pot reaction of diselenides with Baylis-Hillman adducts in the presence of samarium metal-trimethylsilyl chloride under mild conditions. Presumably, the diselenides are cleaved by Sm/TMSCl system to form selenide anions, which then undergo S(N)2' substitution of Baylis-Hillman adducts to produce the (Z)-allyl selenides.
Magnetic Resonance Spectroscopy ; Molecular Structure ; Organoselenium Compounds ; chemistry ; Selenium Compounds ; chemical synthesis ; chemistry ; Stereoisomerism

OBJECTIVETo assess how trace element selenium and B27 supplements affect the neural stem cell (NSc) differentiation in vitro.

METHODSThe development and differentiation of NSc from the newborn rat were observed with primary culture and subculture during treating by sodium-selenite, and selenium-methyl-cysteine (SMC). The immunocytochemistry techniques were used to identify the NSc and mature protein expression with neuron marker beta-tubulin, astrocyte marker GFAP, and oligodendrocyte marker CNPase. The neurosphere morphology and neurite outgrowth were observed.

RESULTSAdding the complete B-27 serum-free supplement, Selenium could promote the neurosphere viability, development and differentiation. Without selenium and B-27, neurosphere could not survive and differentiate. Without B-27 in the medium but there containing selenium, the neurosphere could promote the viability and development into neuron, astrocyte and oligodendrocyte, as compared with the no-containing B-27 and selenium groups, these differentiated cells might have more quantity, more branches and better morphological nerve net. The count of the neuron, astrocyte and oligodendrocyte was 11.2/Hp, 16.1/Hp and 9.3/Hp.

CONCLUSIONSThe selenium should be very important for neural stem cells' survival. Selenium could promote the neurosphere cells differentiation and development.

Animals ; Animals, Newborn ; Cell Differentiation ; drug effects ; Cell Survival ; drug effects ; Cells, Cultured ; Culture Media, Serum-Free ; pharmacology ; Cysteine ; analogs & derivatives ; pharmacology ; Female ; Glial Fibrillary Acidic Protein ; metabolism ; Immunohistochemistry ; Male ; Neurons ; cytology ; drug effects ; metabolism ; Organoselenium Compounds ; pharmacology ; Rats ; Rats, Wistar ; Selenium ; pharmacology ; Selenocysteine ; analogs & derivatives ; Sodium Selenite ; pharmacology ; Stem Cells ; cytology ; drug effects ; metabolism ; Tubulin ; metabolism

AIMTo synthesize the selenophosphocholine analogues containing tegafur and test their antitumor activities.

METHODSThe cyclic glyceroselenophospholopid conjugate of tegafur was synthesized by the reaction of hexaethylphosphorous triamide with N1-(2-furanidyl)-N3-(hydroxyalkyl)-5-fluyorouracil and 1-O-hexadecyl glycerol as well as selenium in one-pot. Cyclic glyceroselenophospholopid conjugate of tegafur reacted with triethylamine to give title compounds.

RESULTSSix new compounds have been synthesized. Their structures were confirmed by 1H NMR, 13P NMR and elemental analysis. Antitumor activity of the title compounds against PGA1 was tested.

CONCLUSIONThe reaction of triethylamine with cyclic glyceroselenophospholopid conjugate of tegafur very readily occurred, which was finished within 2 h at room temperature. The opening-ring products of trans isomers showed antimutor activity against human uriaryl bladder cancer cell more effective than that of the tegafur.

Antineoplastic Agents ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Humans ; Magnetic Resonance Spectroscopy ; Organoselenium Compounds ; chemical synthesis ; pharmacology ; Phosphorylcholine ; analogs & derivatives ; Tegafur ; chemical synthesis ; pharmacology ; Urinary Bladder Neoplasms ; drug therapy ; pathology

To investigate the reversal effect of methylseleninic acid on cisplatin (DDP)-resistant ovarian cancer cells and the underlying mechanisms.
 Methods: SKOV3/DDP cells were incubated with cisplatin at different concentrations for 48 h, then the proliferation rate of SKOV3/DDP cells was detected by MTT assays, and the expression of β-catenin in SKOV3/DDP cells was examined by Western blot. The inhibitory effect of methyl-seleninic acid (MSA) combined with DDP at different concentrations on SKOV3/DDP cells was assayed by MTT method. Western blot was used to detect the expression of β-catenin protein in the cells.
 Results: The inhibitory rate for proliferation in DDP-treated SKOV3/DDP cells with different concentrations is lower than that in the SKOV3 cells (P<0.05); β-catenin expression in SKOV3/DDP cells was significantly higher than that in the SKOV3 cells (P<0.05). The inhibitory rate for proliferation in SKOV3/DDP cells with different concentrations of MSA was increased with the increase in concentration (P<0.05). The inhibitory rate for proliferation in SKOV3/DDP cells with 2 or 6 μmol/L MSA plus cisplatin was lower than that in cisplatin alone group (P<0.05). β-catenin expression in SKOV3 /DDP cells with 2 or 6 μmol/L MSA plus cisplatin was higher than that in the cisplatin alone group (P<0.05).
 Conclusion: MSA can reverse cisplatin resistance on SKOV3 / DDP cells, which may be related to the decrease in β-catenin expression.
Antineoplastic Agents ; pharmacology ; Carcinoma ; physiopathology ; Cell Line, Tumor ; physiology ; Cell Proliferation ; drug effects ; Cisplatin ; pharmacology ; Drug Resistance, Neoplasm ; drug effects ; genetics ; Female ; Humans ; Organoselenium Compounds ; pharmacology ; Ovarian Neoplasms ; physiopathology ; beta Catenin ; drug effects ; metabolism

Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)]ethane (BBSKE), a novel TrxR inhibitor, were investigated on human leukemia cell lines HL-60 and K562. BBSKE treatment induced cell growth inhibition and apoptosis in both cell lines. Apoptosis induced by BBSKE is through Bcl-2/Bax and caspase-3 pathways. Ehrlich's ascites carcinoma-bearing mice were used to investigate the anti-tumor effect of BBSKE in vivo. Tumor-bearing mice treated with BBSKE showed an increase of life span with a comparable effect to cyclophosphamide (CTX). These results suggest a potential usage of BBSKE as a therapeutic agent against non-solid tumors.
Apoptosis ; drug effects ; Bridged Bicyclo Compounds, Heterocyclic ; pharmacology ; Cell Proliferation ; drug effects ; Enzyme Inhibitors ; pharmacology ; HL-60 Cells ; Humans ; K562 Cells ; Organoselenium Compounds ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; physiology ; Thioredoxin-Disulfide Reductase ; antagonists & inhibitors ; bcl-2-Associated X Protein ; physiology

This study is to elucidate the metabolic pathway of 1,2-[bis (1,2-benzisoselenazolone-3 (2H)-ketone)]-ethane (BBSKE) in rats. Rats were administrated with a single dose of BBSKE 200 mg x kg(-1). The metabolites in rat urine, feces, bile and plasma were identified by LC-MSn analysis. The characterization of fragment ions from LC-MSn chromatography and mass spectrometry was applied to the investigation of structures of metabolites. Three phase I metabolites were detected in rat urine and feces. Two of them were also found in plasma and one existed in bile. These products were derived from oxidized, methylated and S-methylated BBSKE, separately. One phase II glucuronide of BBSKE was also found in bile. Therefore, it is possible that BBSKE was metabolized by oxidization, methylation and glucuronidation.
Administration, Oral ; Animals ; Antineoplastic Agents ; administration & dosage ; blood ; metabolism ; urine ; Bile ; metabolism ; Bridged Bicyclo Compounds, Heterocyclic ; administration & dosage ; blood ; metabolism ; urine ; Chromatography, Liquid ; Feces ; chemistry ; Male ; Organoselenium Compounds ; administration & dosage ; blood ; metabolism ; urine ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Electrospray Ionization

The thioredoxin system plays a role in a variety of physiological functions, including cell growth, differentiation, apoptosis, tumorigenesis, and immunity. We previously confirmed that butaselen (BS), a novel thioredoxin reductase inhibitor, can inhibit the growth of various human cancer cell lines, yet the underlying mechanism remains elusive. In this study, we investigated the anti-tumor effect of BS in vivo through regulating the immune system of KM mice. We found that BS inhibits tumor proliferation by promoting the activation of splenic lymphocytes in mice. BS can elevate the percentage of CD₄^-CD₈⁺ T lymphocytes and the secretion of downstream cytokines in mice via down-regulating the expression of programmed death-ligand 1 (PD-L1) on the tumor cells' surface in vivo. Further study in HepG2 and BEL-7402 cells showed that decrease of PD-L1 level after BS treatment was achieved by inhibiting signal transducer and activator of transcription 3 (STAT3) phosphorylation. Taken together, our results suggest that BS has a role in promoting the immune response by reducing PD-L1 expression via the STAT3 pathway, and subsequently suppresses tumorigenesis.
Animals ; Antineoplastic Agents/pharmacology* ; B7-H1 Antigen/antagonists & inhibitors* ; Benzene Derivatives/therapeutic use* ; CD8-Positive T-Lymphocytes/drug effects* ; Hep G2 Cells ; Humans ; Liver Neoplasms/pathology* ; Male ; Mice ; Organoselenium Compounds/therapeutic use* ; STAT3 Transcription Factor/physiology* ; Thioredoxin-Disulfide Reductase/antagonists & inhibitors* ; Tumor Burden/drug effects*

Apoptosis ; drug effects ; Cell Division ; drug effects ; Esophageal Neoplasms ; pathology ; Humans ; Selenomethionine ; pharmacology ; Tumor Cells, Cultured

OBJECTIVEHuman selenoprotein P (HSelP) is unique protein that contains 10 selenocysteines encoded by 10 inframe UGA, which typically function as stop codon. The function of HSelP remains unclear, in part due to the inability to express it by gene recombinant technique. This study is to investigate expression and purification of recombinant HSelP in prokaryotic expression system, and its activity to induce apoptosis in vitro.

METHODSThe shorter HSelP isoform was cloned. After the selenocysteine (SeCys) at 40th position from N terminus of the HSelP shorter isoform was mutated into cysteine by PCR, it was expressed in E. coli. The expressed product was purified with DEAE column and identified by Western blot. Subsequently, its function on induction of mitochondrial apoptotic activity was studied.

RESULTSThe mutant HSelP shorter isoform expressed in prokaryotic system was purified by DEAE column to 90% homogeneity. The purified product, HSelP280m, induced the opening of mitochondrial permeability transition pore (PTP) and decreased the transmembrane potential in a dose-dependent manner. These events could be abolished by PTP specific inhibitors.

CONCLUSIONHSelP280m can induce the opening of mitochondrial PTP, which provides a basis for investigating the structure and function of recombinant HSelP.

Animals ; Apoptosis ; drug effects ; Cloning, Molecular ; Cysteine ; genetics ; Escherichia coli ; metabolism ; Humans ; Ion Channels ; drug effects ; Male ; Membrane Potentials ; drug effects ; Mice ; Mice, Inbred BALB C ; Mitochondria, Liver ; physiology ; Mitochondrial Membrane Transport Proteins ; Mutation ; Protein Isoforms ; Proteins ; genetics ; metabolism ; pharmacology ; Selenium ; Selenocysteine ; genetics ; Selenoprotein P ; Selenoproteins