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Thioredoxin Confers Intrinsic Resistance to Cytostatic Drugs in Human Glioma Cells
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| Zeitschriftentitel: | International Journal of Molecular Sciences |
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| Personen und Körperschaften: | , , , , , |
| In: | International Journal of Molecular Sciences, 19, 2018, 10, S. 2874 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
MDPI AG
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| Schlagwörter: |
| author_facet |
Haas, Bodo Schütte, Lena Wos-Maganga, Maria Weickhardt, Sandra Timmer, Marco Eckstein, Niels Haas, Bodo Schütte, Lena Wos-Maganga, Maria Weickhardt, Sandra Timmer, Marco Eckstein, Niels |
|---|---|
| author |
Haas, Bodo Schütte, Lena Wos-Maganga, Maria Weickhardt, Sandra Timmer, Marco Eckstein, Niels |
| spellingShingle |
Haas, Bodo Schütte, Lena Wos-Maganga, Maria Weickhardt, Sandra Timmer, Marco Eckstein, Niels International Journal of Molecular Sciences Thioredoxin Confers Intrinsic Resistance to Cytostatic Drugs in Human Glioma Cells Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis |
| author_sort |
haas, bodo |
| spelling |
Haas, Bodo Schütte, Lena Wos-Maganga, Maria Weickhardt, Sandra Timmer, Marco Eckstein, Niels 1422-0067 MDPI AG Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis http://dx.doi.org/10.3390/ijms19102874 <jats:p>Thioredoxin (Trx) overexpression is known to be a cause of chemotherapy resistance in various tumor entities. However, Trx effects on resistance are complex and depend strictly on tissue type. In the present study, we analyzed the impact of the Trx system on intrinsic chemoresistance of human glioblastoma multiforme (GBM) cells to cytostatic drugs. Resistance of GBM cell lines and primary cells to drugs and signaling inhibitors was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Impact of Trx inhibition on apoptosis was investigated by proteome profiling of a subset of proteins and annexin V apoptosis assays. Trx-interacting protein (TXNIP) was overexpressed by transfection and protein expression was determined by immunoblotting. Pharmacological inhibition of Trx by 1-methyl-2-imidazolyl-disulfide (PX-12) reduced viability of three GBM cell lines, induced expression of active caspase-3, and reduced phosphorylation of AKT-kinase and expression of β-catenin. Sensitivity to cisplatin could be restored by both PX-12 and recombinant expression of the upstream Trx inhibitor TXNIP, respectively. In addition, PX-12 also sensitized primary human GBM cells to temozolomide. Combined inhibition of Trx and the phosphatidylinositide 3-kinase (PI3K) pathway resulted in massive cell death. We conclude that the Trx system and the PI3K pathway act as a sequential cascade and could potentially present a new drug target.</jats:p> Thioredoxin Confers Intrinsic Resistance to Cytostatic Drugs in Human Glioma Cells International Journal of Molecular Sciences |
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| title |
Thioredoxin Confers Intrinsic Resistance to Cytostatic Drugs in Human Glioma Cells |
| title_unstemmed |
Thioredoxin Confers Intrinsic Resistance to Cytostatic Drugs in Human Glioma Cells |
| title_full |
Thioredoxin Confers Intrinsic Resistance to Cytostatic Drugs in Human Glioma Cells |
| title_fullStr |
Thioredoxin Confers Intrinsic Resistance to Cytostatic Drugs in Human Glioma Cells |
| title_full_unstemmed |
Thioredoxin Confers Intrinsic Resistance to Cytostatic Drugs in Human Glioma Cells |
| title_short |
Thioredoxin Confers Intrinsic Resistance to Cytostatic Drugs in Human Glioma Cells |
| title_sort |
thioredoxin confers intrinsic resistance to cytostatic drugs in human glioma cells |
| topic |
Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis |
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http://dx.doi.org/10.3390/ijms19102874 |
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2018 |
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2874 |
| description |
<jats:p>Thioredoxin (Trx) overexpression is known to be a cause of chemotherapy resistance in various tumor entities. However, Trx effects on resistance are complex and depend strictly on tissue type. In the present study, we analyzed the impact of the Trx system on intrinsic chemoresistance of human glioblastoma multiforme (GBM) cells to cytostatic drugs. Resistance of GBM cell lines and primary cells to drugs and signaling inhibitors was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Impact of Trx inhibition on apoptosis was investigated by proteome profiling of a subset of proteins and annexin V apoptosis assays. Trx-interacting protein (TXNIP) was overexpressed by transfection and protein expression was determined by immunoblotting. Pharmacological inhibition of Trx by 1-methyl-2-imidazolyl-disulfide (PX-12) reduced viability of three GBM cell lines, induced expression of active caspase-3, and reduced phosphorylation of AKT-kinase and expression of β-catenin. Sensitivity to cisplatin could be restored by both PX-12 and recombinant expression of the upstream Trx inhibitor TXNIP, respectively. In addition, PX-12 also sensitized primary human GBM cells to temozolomide. Combined inhibition of Trx and the phosphatidylinositide 3-kinase (PI3K) pathway resulted in massive cell death. We conclude that the Trx system and the PI3K pathway act as a sequential cascade and could potentially present a new drug target.</jats:p> |
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| author | Haas, Bodo, Schütte, Lena, Wos-Maganga, Maria, Weickhardt, Sandra, Timmer, Marco, Eckstein, Niels |
| author_facet | Haas, Bodo, Schütte, Lena, Wos-Maganga, Maria, Weickhardt, Sandra, Timmer, Marco, Eckstein, Niels, Haas, Bodo, Schütte, Lena, Wos-Maganga, Maria, Weickhardt, Sandra, Timmer, Marco, Eckstein, Niels |
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| description | <jats:p>Thioredoxin (Trx) overexpression is known to be a cause of chemotherapy resistance in various tumor entities. However, Trx effects on resistance are complex and depend strictly on tissue type. In the present study, we analyzed the impact of the Trx system on intrinsic chemoresistance of human glioblastoma multiforme (GBM) cells to cytostatic drugs. Resistance of GBM cell lines and primary cells to drugs and signaling inhibitors was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Impact of Trx inhibition on apoptosis was investigated by proteome profiling of a subset of proteins and annexin V apoptosis assays. Trx-interacting protein (TXNIP) was overexpressed by transfection and protein expression was determined by immunoblotting. Pharmacological inhibition of Trx by 1-methyl-2-imidazolyl-disulfide (PX-12) reduced viability of three GBM cell lines, induced expression of active caspase-3, and reduced phosphorylation of AKT-kinase and expression of β-catenin. Sensitivity to cisplatin could be restored by both PX-12 and recombinant expression of the upstream Trx inhibitor TXNIP, respectively. In addition, PX-12 also sensitized primary human GBM cells to temozolomide. Combined inhibition of Trx and the phosphatidylinositide 3-kinase (PI3K) pathway resulted in massive cell death. We conclude that the Trx system and the PI3K pathway act as a sequential cascade and could potentially present a new drug target.</jats:p> |
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| spelling | Haas, Bodo Schütte, Lena Wos-Maganga, Maria Weickhardt, Sandra Timmer, Marco Eckstein, Niels 1422-0067 MDPI AG Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis http://dx.doi.org/10.3390/ijms19102874 <jats:p>Thioredoxin (Trx) overexpression is known to be a cause of chemotherapy resistance in various tumor entities. However, Trx effects on resistance are complex and depend strictly on tissue type. In the present study, we analyzed the impact of the Trx system on intrinsic chemoresistance of human glioblastoma multiforme (GBM) cells to cytostatic drugs. Resistance of GBM cell lines and primary cells to drugs and signaling inhibitors was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Impact of Trx inhibition on apoptosis was investigated by proteome profiling of a subset of proteins and annexin V apoptosis assays. Trx-interacting protein (TXNIP) was overexpressed by transfection and protein expression was determined by immunoblotting. Pharmacological inhibition of Trx by 1-methyl-2-imidazolyl-disulfide (PX-12) reduced viability of three GBM cell lines, induced expression of active caspase-3, and reduced phosphorylation of AKT-kinase and expression of β-catenin. Sensitivity to cisplatin could be restored by both PX-12 and recombinant expression of the upstream Trx inhibitor TXNIP, respectively. In addition, PX-12 also sensitized primary human GBM cells to temozolomide. Combined inhibition of Trx and the phosphatidylinositide 3-kinase (PI3K) pathway resulted in massive cell death. We conclude that the Trx system and the PI3K pathway act as a sequential cascade and could potentially present a new drug target.</jats:p> Thioredoxin Confers Intrinsic Resistance to Cytostatic Drugs in Human Glioma Cells International Journal of Molecular Sciences |
| spellingShingle | Haas, Bodo, Schütte, Lena, Wos-Maganga, Maria, Weickhardt, Sandra, Timmer, Marco, Eckstein, Niels, International Journal of Molecular Sciences, Thioredoxin Confers Intrinsic Resistance to Cytostatic Drugs in Human Glioma Cells, Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis |
| title | Thioredoxin Confers Intrinsic Resistance to Cytostatic Drugs in Human Glioma Cells |
| title_full | Thioredoxin Confers Intrinsic Resistance to Cytostatic Drugs in Human Glioma Cells |
| title_fullStr | Thioredoxin Confers Intrinsic Resistance to Cytostatic Drugs in Human Glioma Cells |
| title_full_unstemmed | Thioredoxin Confers Intrinsic Resistance to Cytostatic Drugs in Human Glioma Cells |
| title_short | Thioredoxin Confers Intrinsic Resistance to Cytostatic Drugs in Human Glioma Cells |
| title_sort | thioredoxin confers intrinsic resistance to cytostatic drugs in human glioma cells |
| title_unstemmed | Thioredoxin Confers Intrinsic Resistance to Cytostatic Drugs in Human Glioma Cells |
| topic | Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis |
| url | http://dx.doi.org/10.3390/ijms19102874 |