Abstract
Malignant mesothelioma (MM) is a fatal type of cancer. We studied the role of the redox-active protein thioredoxin-1 (Trx-1) in apoptosis induced in MM cells and their non-malignant counterparts (Met-5A) by alpha-tocopheryl succinate (alpha-TOS) and TNF-related apoptosis-inducing ligand (TRAIL). MM cells were susceptible to alpha-TOS and less to TRAIL, while Met-5A cells were susceptible to TRAIL and resistant to alpha-TOS. MM cells expressed very low level of the Trx-1 protein, which was high in Met-5A cells, while the level of Trx-1 mRNA was similar in all cell lines. Downregulation of Trx-1 further sensitised Met-5A cells to TRAIL but not to alpha-TOS. Our data suggest that the role of Trx-1 in apoptosis modulation is unrelated to its anti-oxidant properties.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects*
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Apoptosis Regulatory Proteins / pharmacology*
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Cell Line, Tumor
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DNA, Mitochondrial / genetics
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Humans
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Membrane Glycoproteins / pharmacology*
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Mesothelioma / genetics
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Mesothelioma / metabolism*
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Mesothelioma / pathology*
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RNA, Small Interfering / genetics
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TNF-Related Apoptosis-Inducing Ligand
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Thioredoxins / genetics
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Thioredoxins / metabolism*
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Tocopherols
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Tumor Necrosis Factor-alpha / pharmacology*
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Vitamin E / analogs & derivatives*
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Vitamin E / pharmacology
Substances
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Apoptosis Regulatory Proteins
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DNA, Mitochondrial
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Membrane Glycoproteins
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RNA, Small Interfering
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human
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Tumor Necrosis Factor-alpha
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Vitamin E
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Thioredoxins
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Tocopherols