The Experts below are selected from a list of 270 Experts worldwide ranked by ideXlab platform
Tianfeng Chen - One of the best experts on this subject based on the ideXlab platform.
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Enhancement of auranofin-induced apoptosis in MCF-7 human breast cells by selenocystine, a synergistic inhibitor of thioredoxin reductase. PLoS One 2013
2016Co-Authors: Chaoran Liu, Yum-shing Wong, Wenjie Zheng, Zhong Liu, Sai-ming Ngai, Yibo Zhang, Tianfeng ChenAbstract:Thioredoxin system plays an important role in regulation of intracellular redox balance and various signaling pathways. Thioredoxin reductase (TrxR) is overexpressed in many cancer cells and has been identified as a potential target of anticancer drugs. Auranofin (AF) is potent TrxR inhibitor with novel in vitro and in vivo anticancer activities. Selenocystine (SeC) is a nutritionally available Selenoamino Acid with selective anticancer effects through induction of apoptosis. In the present study, we demonstrated the synergistic effects and the underlying molecular mechanisms of SeC in combination with AF on MCF-7 human breast cancer cells. The results showed that SeC and AF synergistically inhibited the cancer cell growth through induction of ROS-dependent apoptosis with the involvement of mitochondrial dysfunction. DNA damage-mediated p53 phosphorylation and down-regulation of phosphorylated AKT and ERK also contributed to cell apoptosis. Moreover, we demonstrated the important role of TrxR activity in the synergistic action of SeC and AF. Taken together, our results suggest the strategy to use SeC and AF in combination could be a highly efficient way to achieve anticancer synergism by targeting TrxR
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Rational design and fabrication of a cancer-targeted chitosan nanocarrier to enhance selective cellular uptake and anticancer efficacy of selenocystine
Journal of Materials Chemistry B, 2015Co-Authors: Jinhui Zhang, Wenjie Zheng, Tianfeng ChenAbstract:The rational design and fabrication of nanodelivery systems to encapsulate drugs has been proven to be a promising and effective strategy for cancer therapy. Selenocystine (SeC), a naturally occurring Selenoamino Acid, has received more and more attention due to its novel pharmacological properties in the treatments of cancers. In this study, we fabricated a cancer-targeted nanodrug delivery system by encapsulating SeC into chitosan (CS) nanoparticles with folate surface decoration (FA–SeC–CSNPs) and evaluated its antiproliferative activities. The nanosystem entered the cells through endocytosis and released SeC in lysosomes under an Acidic environment. Compared with SeC–CSNPs and SeC, FA–SeC–CSNPs significantly inhibited the growth of HeLa human cervical cancer cells that overexpressed folate receptors through the induction of apoptosis with the involvement of PARP cleavage and caspase activation. Moreover, FA–SeC–CSNPs also significantly suppressed the migration and invasion of HeLa cells in a dose-dependent manner. Furthermore, the intracellular nanosystem triggered the overproduction of reactive oxygen species (ROS) as early as 25 min after treatment, which activated various downstream signaling pathways such as p53, AKT and MAPKs to induce the cell death. Taken together, this study demonstrates a strategy for rational design of a cancer-targeted nanosystem loaded with selenocompounds to achieve selective cellular uptake and enhanced anticancer efficacy.
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Strategy to enhance the therapeutic effect of doxorubicin in human hepatocellular carcinoma by selenocystine, a synergistic agent that regulates the ROS-mediated signaling.
Oncotarget, 2014Co-Authors: Cundong Fan, Wenjie Zheng, Yum-shing Wong, Tianfeng ChenAbstract:// Cundong Fan 1 , Wenjie Zheng 1 , Xiaoyan Fu 1 , Xiaoling Li 1 , Yum-Shing Wong 2 , Tianfeng Chen 1 1 Department of Chemistry, Jinan University, Guangzhou 510632, China 2 School of Life Sciences and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong S.A.R., China Correspondence: Tianfeng Chen, email: // Keywords : selenocystine; synergism; doxorubicin; apoptosis; reactive oxygen species Received : January 1, 2014 Accepted : March 24, 2014 Published : March 25, 2014 Abstract Doxorubicin-based chemotherapy represents one of the most effective ways in combating human cancers. However, its clinical use is limited by severe side effects. Selenocystine (SeC) is a natural available Selenoamino Acid with novel anticancer efficacy. In this study, we used SeC to sensitize HepG2 human hepatocellular carcinoma (HCC) cells to DOX, and to achieve anticancer synergism in vitro and in vivo. Treatment with DOX dose-dependently reduced HepG2 cell viability through initiating cell apoptosis and strong G2/M phase cell cycle arrest. Mechanistic studies indicated that this sensitization of SeC to DOX was achieved by triggering inactivation of ERK and AKT and DNA damage through reactive oxygen species (ROS) overproduction. Pretreatment with inhibitors of ERK and AKT markedly enhanced combined treatment-induced cell killing, indicating that combined treatment-induced HCC cell killing with ERK- and AKT-dependent manner. Furthermore, inhibition of ROS effectively attenuated combined treatment-induced DNA damage and inactivation of ERK and AKT. Additionally, xenograft hepatocellular carcinoma growth was also effectively inhibited by combined treatment through induction of cell apoptosis in vivo. Taken together, our results suggest that the strategy to use SeC and DOX in combination could be a highly efficient way to achieve anticancer synergism against HCC.
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selenocystine potentiates cancer cell apoptosis induced by 5 fluorouracil by triggering reactive oxygen species mediated dna damage and inactivation of the erk pathway
Free Radical Biology and Medicine, 2013Co-Authors: Cundong Fan, Yum-shing Wong, Wenjie Zheng, Yibo Zhang, Jingjing Chen, Yi Wang, Wenqiang Cao, Tianfeng ChenAbstract:5-Fluorouracil (5-FU)-based chemotherapy as a first-line treatment is quite limited, because of its inefficiency and clinical resistance to it. The search for chemosensitizers that could augment its efficiency and overcome the drug resistance to 5-FU has kindled great interest among scientists. Selenocystine (SeC), a naturally occurring Selenoamino Acid, displayed broad-spectrum anticancer activity in our previous studies. This study demonstrates that SeC acts as an effective enhancer of 5-FU-induced apoptosis in A375 human melanoma cells through induction of mitochondria-mediated apoptosis with the involvement of DNA damage-mediated p53 phosphorylation and ERK inactivation. Pretreatment of the cells with SeC significantly enhanced 5-FU-induced loss of mitochondrial membrane potential (∆ψm) by regulating the expression levels of Bcl-2 family proteins. SeC and 5-FU in combination also triggered cell oxidative stress through regulation of the intracellular redox system and led to DNA damage and inactivation of ERK and AKT. Moreover, inhibitors of ERK and AKT effectively enhanced the apoptotic cell death induced by the combined treatment. However, pretreatment of the cells with glutathione reversed the apoptosis induced by SeC and 5-FU and recovered the expression of ERK and AKT inactivation, which revealed the important role of reactive oxygen species in cell apoptosis and regulation of ERK and AKT pathways. Taken together, our results suggest that a strategy of using SeC and 5-FU in combination could be a highly efficient way to achieve anticancer synergism.
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Enhancement of Auranofin-Induced Apoptosis in MCF-7 Human Breast Cells by Selenocystine, a Synergistic Inhibitor of Thioredoxin Reductase
PLoS ONE, 2013Co-Authors: Chaoran Liu, Yum-shing Wong, Wenjie Zheng, Zhong Liu, Sai-ming Ngai, Yibo Zhang, Tianfeng ChenAbstract:Thioredoxin system plays an important role in regulation of intracellular redox balance and various signaling pathways. Thioredoxin reductase (TrxR) is overexpressed in many cancer cells and has been identified as a potential target of anticancer drugs. Auranofin (AF) is potent TrxR inhibitor with novel in vitro and in vivo anticancer activities. Selenocystine (SeC) is a nutritionally available Selenoamino Acid with selective anticancer effects through induction of apoptosis. In the present study, we demonstrated the synergistic effects and the underlying molecular mechanisms of SeC in combination with AF on MCF-7 human breast cancer cells. The results showed that SeC and AF synergistically inhibited the cancer cell growth through induction of ROS-dependent apoptosis with the involvement of mitochondrial dysfunction. DNA damage-mediated p53 phosphorylation and down-regulation of phosphorylated AKT and ERK also contributed to cell apoptosis. Moreover, we demonstrated the important role of TrxR activity in the synergistic action of SeC and AF. Taken together, our results suggest the strategy to use SeC and AF in combination could be a highly efficient way to achieve anticancer synergism by targeting TrxR.
Yasumitsu Ogra - One of the best experts on this subject based on the ideXlab platform.
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Distribution and metabolism of selenohomolanthionine labeled with a stable isotope
Analytical and Bioanalytical Chemistry, 2011Co-Authors: Yasumi Anan, Takahiro Mikami, Yoshiro Tsuji, Yasumitsu OgraAbstract:The distribution and metabolism of selenohomolanthionine (4,4′-selenobis[2-aminobutanoic Acid], SeHLan), a newly identified Selenoamino Acid in selenized Japanese pungent radish, were evaluated by administering ^77Se-labeled SeHLan at a dose of 25 μg/kg body weight in rats. Exogenous ^77Se of SeHLan was preferably distributed to the kidneys and remained in the intact form for up to 6 h after dosing. The accumulation in the kidneys is one of the specific characteristics of SeHLan, differing from other Selenoamino Acids, such as selenomethionine and Se -methylselenocysteine, which preferably accumulate in the pancreas. The intact form of SeHLan was detected in the serum and kidney supernatant but not in the urine, suggesting that the amount of exogenous Se that was distributed to the kidneys was within metabolic capacity. Indeed, the exogenous Se was converted into two urinary metabolites, Se -methylseleno- N -acetyl-galactosamine and trimethylselenonium. Exogenous Se was also detected in several selenoproteins, including selenoprotein P and extracellular glutathione peroxidase. SeHLan is expected to be a potential supplemental source of Se because its distribution differs from that of selenomethionine and Se -methylselenocysteine. Simultaneous detection of exogenous and endogenous Se metabolites using a stable isotope labeled Se compound.
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Distribution and metabolism of selenohomolanthionine labeled with a stable isotope
Analytical and bioanalytical chemistry, 2010Co-Authors: Yasumi Anan, Takahiro Mikami, Yoshiro Tsuji, Yasumitsu OgraAbstract:The distribution and metabolism of selenohomolanthionine (4,4′-selenobis[2-aminobutanoic Acid], SeHLan), a newly identified Selenoamino Acid in selenized Japanese pungent radish, were evaluated by administering 77Se-labeled SeHLan at a dose of 25 μg/kg body weight in rats. Exogenous 77Se of SeHLan was preferably distributed to the kidneys and remained in the intact form for up to 6 h after dosing. The accumulation in the kidneys is one of the specific characteristics of SeHLan, differing from other Selenoamino Acids, such as selenomethionine and Se-methylselenocysteine, which preferably accumulate in the pancreas. The intact form of SeHLan was detected in the serum and kidney supernatant but not in the urine, suggesting that the amount of exogenous Se that was distributed to the kidneys was within metabolic capacity. Indeed, the exogenous Se was converted into two urinary metabolites, Se-methylseleno-N-acetyl-galactosamine and trimethylselenonium. Exogenous Se was also detected in several selenoproteins, including selenoprotein P and extracellular glutathione peroxidase. SeHLan is expected to be a potential supplemental source of Se because its distribution differs from that of selenomethionine and Se-methylselenocysteine.
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comparison of selenohomolanthionine and selenomethionine in terms of selenium distribution and toxicity in rats by bolus administration
Metallomics, 2010Co-Authors: Yoshiro Tsuji, Takahiro Mikami, Yasumi Anan, Yasumitsu OgraAbstract:The distribution and metabolism of selenohomolanthionine (4,4′-selenobis[2-aminobutanoic Acid], SeHLan), a newly identified Selenoamino Acid in selenized Japanese pungent radish, were compared with those of selenomethionine (SeMet) in rats. Either Selenoamino Acid was injected intravenously at a bolus dose of 1.0 mg Se/kg body weight. SeMet was preferably accumulated in the pancreas, increasing the serum amylase level, an index of pancreatic damage. SeHLan was preferably accumulated in the kidneys, raising the serum creatinine level, an index of kidney damage. On the other hand, the levels of two major urinary selenometabolites, i.e., Se-methylseleno-N-acetyl-galactosamine and trimethylselenonium, were comparable between SeHLan- and SeMet-administered rats, suggesting that there may be no differences in the efficiency of metabolism of these two Selenoamino Acids to the urinary selenometabolites despite the difference in distribution. SeHLan is expected to be a potential supplemental source of Se without inducing the onset of pancreatic damage. The specific toxicity of SeHLan to the kidneys may be avoided if its dose is lower than the one used in the present study.
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Speciation of selenium in selenium-enriched seeds, buckwheat (Fagopyrum esculentum Moench) and quinoa (Chenopodium quinoa Willdenow)
European Food Research and Technology, 2008Co-Authors: Takashi Kitaguchi, Yasumitsu Ogra, Yuji Iwashita, Kazuo T SuzukiAbstract:Buckwheat ( Fagopyrum esculentum Moench) and quinoa ( Chenopodium quinoa Willdenow) are widely used as food ingredients. The nutritional characteristics of these plants, i.e., high contents of proteins and amino Acids suggest that selenium (Se) is preserved as Selenoamino Acid derivatives, in particular, selenomethionine (SeMet) in proteins, similar to selenized yeast. Therefore, buckwheat and quinoa are expected to be a good nutritional source of Se. Selenized buckwheat and quinoa were cultivated on Se-fortified soil using sparingly soluble Se salts, such as barium selenate and barium selenite. Se concentration in the edible parts of these plants was determined, and Se extraction efficiency with enzyme or alkali was evaluated. In addition, the chemical species of Se in the low molecular weight fraction of these plants were determined by HPLC-ICP-MS. Total Se concentrations in the edible parts of selenized buckwheat and quinoa were 170.4 ± 2.9 μg/g and 102.7 ± 2.4 μg/g wet weight, respectively. Thus, these selenized seeds were found to be Se accumulators. The results indicate that Se in selenized buckwheat exists mainly as SeMet, while Se in selenized quinoa exists not only as SeMet but also as selenate (Se(VI)) and non-protein forms.
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determination of selenomethionine and selenocysteine in human serum using speciated isotope dilution capillary hplc inductively coupled plasma collision cell mass spectrometry
Analytical Chemistry, 2004Co-Authors: Jorge Ruiz Encinar, Yasumitsu Ogra, Dirk Schaumlöffel, Ryszard LobinskiAbstract:A method for the accurate determination of Selenoamino Acids in human serum by HPLC−ICPMS was developed using the species-specific isotope dilution analysis principle. A serum sample was enzymatically digested with a mixture of lipase and protease after derivatization of the selenocysteine residues with iodoacetamide. The Selenoamino Acid fraction was isolated by size exclusion LC followed by the separation of selenomethionine and the carboxymethylated selenocysteine by capillary HPLC. The isotope-specific determination of 77Se and 80Se was achieved on-line by ICP collision cell MS allowing the removal of polyatomic interferences. Quantification was carried out by isotope dilution using a 77Se-labeled selenomethionine spike and the determination of the 77Se/80Se ratio in the cHPLC selenomethionine peak. The accurately determined selenomethionine was used as an internal standard for the selenocysteine determination from the same chromatogram. The modification of the previously developed cHPLC−ICPMS interfa...
Yum-shing Wong - One of the best experts on this subject based on the ideXlab platform.
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Enhancement of auranofin-induced apoptosis in MCF-7 human breast cells by selenocystine, a synergistic inhibitor of thioredoxin reductase. PLoS One 2013
2016Co-Authors: Chaoran Liu, Yum-shing Wong, Wenjie Zheng, Zhong Liu, Sai-ming Ngai, Yibo Zhang, Tianfeng ChenAbstract:Thioredoxin system plays an important role in regulation of intracellular redox balance and various signaling pathways. Thioredoxin reductase (TrxR) is overexpressed in many cancer cells and has been identified as a potential target of anticancer drugs. Auranofin (AF) is potent TrxR inhibitor with novel in vitro and in vivo anticancer activities. Selenocystine (SeC) is a nutritionally available Selenoamino Acid with selective anticancer effects through induction of apoptosis. In the present study, we demonstrated the synergistic effects and the underlying molecular mechanisms of SeC in combination with AF on MCF-7 human breast cancer cells. The results showed that SeC and AF synergistically inhibited the cancer cell growth through induction of ROS-dependent apoptosis with the involvement of mitochondrial dysfunction. DNA damage-mediated p53 phosphorylation and down-regulation of phosphorylated AKT and ERK also contributed to cell apoptosis. Moreover, we demonstrated the important role of TrxR activity in the synergistic action of SeC and AF. Taken together, our results suggest the strategy to use SeC and AF in combination could be a highly efficient way to achieve anticancer synergism by targeting TrxR
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Strategy to enhance the therapeutic effect of doxorubicin in human hepatocellular carcinoma by selenocystine, a synergistic agent that regulates the ROS-mediated signaling.
Oncotarget, 2014Co-Authors: Cundong Fan, Wenjie Zheng, Yum-shing Wong, Tianfeng ChenAbstract:// Cundong Fan 1 , Wenjie Zheng 1 , Xiaoyan Fu 1 , Xiaoling Li 1 , Yum-Shing Wong 2 , Tianfeng Chen 1 1 Department of Chemistry, Jinan University, Guangzhou 510632, China 2 School of Life Sciences and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong S.A.R., China Correspondence: Tianfeng Chen, email: // Keywords : selenocystine; synergism; doxorubicin; apoptosis; reactive oxygen species Received : January 1, 2014 Accepted : March 24, 2014 Published : March 25, 2014 Abstract Doxorubicin-based chemotherapy represents one of the most effective ways in combating human cancers. However, its clinical use is limited by severe side effects. Selenocystine (SeC) is a natural available Selenoamino Acid with novel anticancer efficacy. In this study, we used SeC to sensitize HepG2 human hepatocellular carcinoma (HCC) cells to DOX, and to achieve anticancer synergism in vitro and in vivo. Treatment with DOX dose-dependently reduced HepG2 cell viability through initiating cell apoptosis and strong G2/M phase cell cycle arrest. Mechanistic studies indicated that this sensitization of SeC to DOX was achieved by triggering inactivation of ERK and AKT and DNA damage through reactive oxygen species (ROS) overproduction. Pretreatment with inhibitors of ERK and AKT markedly enhanced combined treatment-induced cell killing, indicating that combined treatment-induced HCC cell killing with ERK- and AKT-dependent manner. Furthermore, inhibition of ROS effectively attenuated combined treatment-induced DNA damage and inactivation of ERK and AKT. Additionally, xenograft hepatocellular carcinoma growth was also effectively inhibited by combined treatment through induction of cell apoptosis in vivo. Taken together, our results suggest that the strategy to use SeC and DOX in combination could be a highly efficient way to achieve anticancer synergism against HCC.
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selenocystine potentiates cancer cell apoptosis induced by 5 fluorouracil by triggering reactive oxygen species mediated dna damage and inactivation of the erk pathway
Free Radical Biology and Medicine, 2013Co-Authors: Cundong Fan, Yum-shing Wong, Wenjie Zheng, Yibo Zhang, Jingjing Chen, Yi Wang, Wenqiang Cao, Tianfeng ChenAbstract:5-Fluorouracil (5-FU)-based chemotherapy as a first-line treatment is quite limited, because of its inefficiency and clinical resistance to it. The search for chemosensitizers that could augment its efficiency and overcome the drug resistance to 5-FU has kindled great interest among scientists. Selenocystine (SeC), a naturally occurring Selenoamino Acid, displayed broad-spectrum anticancer activity in our previous studies. This study demonstrates that SeC acts as an effective enhancer of 5-FU-induced apoptosis in A375 human melanoma cells through induction of mitochondria-mediated apoptosis with the involvement of DNA damage-mediated p53 phosphorylation and ERK inactivation. Pretreatment of the cells with SeC significantly enhanced 5-FU-induced loss of mitochondrial membrane potential (∆ψm) by regulating the expression levels of Bcl-2 family proteins. SeC and 5-FU in combination also triggered cell oxidative stress through regulation of the intracellular redox system and led to DNA damage and inactivation of ERK and AKT. Moreover, inhibitors of ERK and AKT effectively enhanced the apoptotic cell death induced by the combined treatment. However, pretreatment of the cells with glutathione reversed the apoptosis induced by SeC and 5-FU and recovered the expression of ERK and AKT inactivation, which revealed the important role of reactive oxygen species in cell apoptosis and regulation of ERK and AKT pathways. Taken together, our results suggest that a strategy of using SeC and 5-FU in combination could be a highly efficient way to achieve anticancer synergism.
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Enhancement of Auranofin-Induced Apoptosis in MCF-7 Human Breast Cells by Selenocystine, a Synergistic Inhibitor of Thioredoxin Reductase
PLoS ONE, 2013Co-Authors: Chaoran Liu, Yum-shing Wong, Wenjie Zheng, Zhong Liu, Sai-ming Ngai, Yibo Zhang, Tianfeng ChenAbstract:Thioredoxin system plays an important role in regulation of intracellular redox balance and various signaling pathways. Thioredoxin reductase (TrxR) is overexpressed in many cancer cells and has been identified as a potential target of anticancer drugs. Auranofin (AF) is potent TrxR inhibitor with novel in vitro and in vivo anticancer activities. Selenocystine (SeC) is a nutritionally available Selenoamino Acid with selective anticancer effects through induction of apoptosis. In the present study, we demonstrated the synergistic effects and the underlying molecular mechanisms of SeC in combination with AF on MCF-7 human breast cancer cells. The results showed that SeC and AF synergistically inhibited the cancer cell growth through induction of ROS-dependent apoptosis with the involvement of mitochondrial dysfunction. DNA damage-mediated p53 phosphorylation and down-regulation of phosphorylated AKT and ERK also contributed to cell apoptosis. Moreover, we demonstrated the important role of TrxR activity in the synergistic action of SeC and AF. Taken together, our results suggest the strategy to use SeC and AF in combination could be a highly efficient way to achieve anticancer synergism by targeting TrxR.
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Comparative Proteomics Analysis of Selenium Responses in Selenium-Enriched Rice Grains
2013Co-Authors: Yu-dong Wang, Sai-ming Ngai, Xu Wang, Yum-shing WongAbstract:By foliar fortification with selenite, selenium (Se)-enriched rice with a higher Se content and grain yield has been generated. However, the regulatory mechanisms of Se response in rice grains remain unknown; therefore, we carried out a comparative proteomics study in Se-enriched rice grains by using two approaches including two-dimensional gel electrophoresis (2-DE)-coupled MALDI-TOF/TOF MS and 1-DE/LC–FTICR–MS-coupled label-free quantification. By comparison between Se treatment and control, 62 and 250 abundance changed proteins were identified from 2-DE and 1-DE, respectively. By functional classification, proteins involved in metabolism, cell redox regulation, and seed nutritional storage were the most highly affected by Se accumulation. The up-regulation of late embryogenesis abundant proteins as well as proteins involved in sucrose synthesis and other metabolism pathways may contribute to the earlier maturation and higher yield of the Se-enriched rice. In addition, there have been six proteins identified to contain Selenoamino Acid modification, which is the first identification of selenoproteins in higher plants. In conclusion, our study provided novel insights into Se response in rice grains at the proteome level, which are expected to be highly useful for dissecting the Se response pathways in rice and for the production of Se-enriched rice in the future
Haijun Yang - One of the best experts on this subject based on the ideXlab platform.
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Visible-Light Photoredox Synthesis of Chiral α-Selenoamino Acids.
Organic letters, 2016Co-Authors: Min Jiang, Haijun YangAbstract:N-Acetoxyphthalimide derivatives of two genetically coded proteinogenic amino Acids, l-aspartic Acid and glutamic Acid, were used as visible light photoredox chiral sources and radical precursors, diorganyl diselenides were used as the radical acceptors, and the diverse chiral α-Selenoamino Acid derivatives were prepared in good yields at room temperature. Furthermore, decarboxylative coupling of N-protected dipeptide active ester with diphenyl diselenide provided the corresponding selenodipeptide. The simple protocol, mild reaction conditions, high efficiency, and chiral keeping of this method make it an important strategy for the synthesis of chiral molecules.
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Visible-Light Photoredox Synthesis of Chiral α‑Selenoamino Acids
2016Co-Authors: Min Jiang, Haijun YangAbstract:N-Acetoxyphthalimide derivatives of two genetically coded proteinogenic amino Acids, l-aspartic Acid and glutamic Acid, were used as visible light photoredox chiral sources and radical precursors, diorganyl diselenides were used as the radical acceptors, and the diverse chiral α-Selenoamino Acid derivatives were prepared in good yields at room temperature. Furthermore, decarboxylative coupling of N-protected dipeptide active ester with diphenyl diselenide provided the corresponding selenodipeptide. The simple protocol, mild reaction conditions, high efficiency, and chiral keeping of this method make it an important strategy for the synthesis of chiral molecules
Wenjie Zheng - One of the best experts on this subject based on the ideXlab platform.
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Enhancement of auranofin-induced apoptosis in MCF-7 human breast cells by selenocystine, a synergistic inhibitor of thioredoxin reductase. PLoS One 2013
2016Co-Authors: Chaoran Liu, Yum-shing Wong, Wenjie Zheng, Zhong Liu, Sai-ming Ngai, Yibo Zhang, Tianfeng ChenAbstract:Thioredoxin system plays an important role in regulation of intracellular redox balance and various signaling pathways. Thioredoxin reductase (TrxR) is overexpressed in many cancer cells and has been identified as a potential target of anticancer drugs. Auranofin (AF) is potent TrxR inhibitor with novel in vitro and in vivo anticancer activities. Selenocystine (SeC) is a nutritionally available Selenoamino Acid with selective anticancer effects through induction of apoptosis. In the present study, we demonstrated the synergistic effects and the underlying molecular mechanisms of SeC in combination with AF on MCF-7 human breast cancer cells. The results showed that SeC and AF synergistically inhibited the cancer cell growth through induction of ROS-dependent apoptosis with the involvement of mitochondrial dysfunction. DNA damage-mediated p53 phosphorylation and down-regulation of phosphorylated AKT and ERK also contributed to cell apoptosis. Moreover, we demonstrated the important role of TrxR activity in the synergistic action of SeC and AF. Taken together, our results suggest the strategy to use SeC and AF in combination could be a highly efficient way to achieve anticancer synergism by targeting TrxR
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Rational design and fabrication of a cancer-targeted chitosan nanocarrier to enhance selective cellular uptake and anticancer efficacy of selenocystine
Journal of Materials Chemistry B, 2015Co-Authors: Jinhui Zhang, Wenjie Zheng, Tianfeng ChenAbstract:The rational design and fabrication of nanodelivery systems to encapsulate drugs has been proven to be a promising and effective strategy for cancer therapy. Selenocystine (SeC), a naturally occurring Selenoamino Acid, has received more and more attention due to its novel pharmacological properties in the treatments of cancers. In this study, we fabricated a cancer-targeted nanodrug delivery system by encapsulating SeC into chitosan (CS) nanoparticles with folate surface decoration (FA–SeC–CSNPs) and evaluated its antiproliferative activities. The nanosystem entered the cells through endocytosis and released SeC in lysosomes under an Acidic environment. Compared with SeC–CSNPs and SeC, FA–SeC–CSNPs significantly inhibited the growth of HeLa human cervical cancer cells that overexpressed folate receptors through the induction of apoptosis with the involvement of PARP cleavage and caspase activation. Moreover, FA–SeC–CSNPs also significantly suppressed the migration and invasion of HeLa cells in a dose-dependent manner. Furthermore, the intracellular nanosystem triggered the overproduction of reactive oxygen species (ROS) as early as 25 min after treatment, which activated various downstream signaling pathways such as p53, AKT and MAPKs to induce the cell death. Taken together, this study demonstrates a strategy for rational design of a cancer-targeted nanosystem loaded with selenocompounds to achieve selective cellular uptake and enhanced anticancer efficacy.
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Strategy to enhance the therapeutic effect of doxorubicin in human hepatocellular carcinoma by selenocystine, a synergistic agent that regulates the ROS-mediated signaling.
Oncotarget, 2014Co-Authors: Cundong Fan, Wenjie Zheng, Yum-shing Wong, Tianfeng ChenAbstract:// Cundong Fan 1 , Wenjie Zheng 1 , Xiaoyan Fu 1 , Xiaoling Li 1 , Yum-Shing Wong 2 , Tianfeng Chen 1 1 Department of Chemistry, Jinan University, Guangzhou 510632, China 2 School of Life Sciences and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong S.A.R., China Correspondence: Tianfeng Chen, email: // Keywords : selenocystine; synergism; doxorubicin; apoptosis; reactive oxygen species Received : January 1, 2014 Accepted : March 24, 2014 Published : March 25, 2014 Abstract Doxorubicin-based chemotherapy represents one of the most effective ways in combating human cancers. However, its clinical use is limited by severe side effects. Selenocystine (SeC) is a natural available Selenoamino Acid with novel anticancer efficacy. In this study, we used SeC to sensitize HepG2 human hepatocellular carcinoma (HCC) cells to DOX, and to achieve anticancer synergism in vitro and in vivo. Treatment with DOX dose-dependently reduced HepG2 cell viability through initiating cell apoptosis and strong G2/M phase cell cycle arrest. Mechanistic studies indicated that this sensitization of SeC to DOX was achieved by triggering inactivation of ERK and AKT and DNA damage through reactive oxygen species (ROS) overproduction. Pretreatment with inhibitors of ERK and AKT markedly enhanced combined treatment-induced cell killing, indicating that combined treatment-induced HCC cell killing with ERK- and AKT-dependent manner. Furthermore, inhibition of ROS effectively attenuated combined treatment-induced DNA damage and inactivation of ERK and AKT. Additionally, xenograft hepatocellular carcinoma growth was also effectively inhibited by combined treatment through induction of cell apoptosis in vivo. Taken together, our results suggest that the strategy to use SeC and DOX in combination could be a highly efficient way to achieve anticancer synergism against HCC.
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selenocystine potentiates cancer cell apoptosis induced by 5 fluorouracil by triggering reactive oxygen species mediated dna damage and inactivation of the erk pathway
Free Radical Biology and Medicine, 2013Co-Authors: Cundong Fan, Yum-shing Wong, Wenjie Zheng, Yibo Zhang, Jingjing Chen, Yi Wang, Wenqiang Cao, Tianfeng ChenAbstract:5-Fluorouracil (5-FU)-based chemotherapy as a first-line treatment is quite limited, because of its inefficiency and clinical resistance to it. The search for chemosensitizers that could augment its efficiency and overcome the drug resistance to 5-FU has kindled great interest among scientists. Selenocystine (SeC), a naturally occurring Selenoamino Acid, displayed broad-spectrum anticancer activity in our previous studies. This study demonstrates that SeC acts as an effective enhancer of 5-FU-induced apoptosis in A375 human melanoma cells through induction of mitochondria-mediated apoptosis with the involvement of DNA damage-mediated p53 phosphorylation and ERK inactivation. Pretreatment of the cells with SeC significantly enhanced 5-FU-induced loss of mitochondrial membrane potential (∆ψm) by regulating the expression levels of Bcl-2 family proteins. SeC and 5-FU in combination also triggered cell oxidative stress through regulation of the intracellular redox system and led to DNA damage and inactivation of ERK and AKT. Moreover, inhibitors of ERK and AKT effectively enhanced the apoptotic cell death induced by the combined treatment. However, pretreatment of the cells with glutathione reversed the apoptosis induced by SeC and 5-FU and recovered the expression of ERK and AKT inactivation, which revealed the important role of reactive oxygen species in cell apoptosis and regulation of ERK and AKT pathways. Taken together, our results suggest that a strategy of using SeC and 5-FU in combination could be a highly efficient way to achieve anticancer synergism.
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Enhancement of Auranofin-Induced Apoptosis in MCF-7 Human Breast Cells by Selenocystine, a Synergistic Inhibitor of Thioredoxin Reductase
PLoS ONE, 2013Co-Authors: Chaoran Liu, Yum-shing Wong, Wenjie Zheng, Zhong Liu, Sai-ming Ngai, Yibo Zhang, Tianfeng ChenAbstract:Thioredoxin system plays an important role in regulation of intracellular redox balance and various signaling pathways. Thioredoxin reductase (TrxR) is overexpressed in many cancer cells and has been identified as a potential target of anticancer drugs. Auranofin (AF) is potent TrxR inhibitor with novel in vitro and in vivo anticancer activities. Selenocystine (SeC) is a nutritionally available Selenoamino Acid with selective anticancer effects through induction of apoptosis. In the present study, we demonstrated the synergistic effects and the underlying molecular mechanisms of SeC in combination with AF on MCF-7 human breast cancer cells. The results showed that SeC and AF synergistically inhibited the cancer cell growth through induction of ROS-dependent apoptosis with the involvement of mitochondrial dysfunction. DNA damage-mediated p53 phosphorylation and down-regulation of phosphorylated AKT and ERK also contributed to cell apoptosis. Moreover, we demonstrated the important role of TrxR activity in the synergistic action of SeC and AF. Taken together, our results suggest the strategy to use SeC and AF in combination could be a highly efficient way to achieve anticancer synergism by targeting TrxR.