Role of thioredoxin-1 in apoptosis induction by alpha-tocopheryl succinate and TNF-related apoptosis-inducing ligand in mesothelioma cells.
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.
Freeman
Ruth E
RE
Apoptosis Research Group, Heart Foundation Research Centre, School of Medical Science, Griffith University, Southport, Qld 9716, Australia.
Neuzil
Jiri
J
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004272:DNA, Mitochondrial / Q000235:genetics; D006801:Humans; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D024505:Tocopherols; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; D004272:DNA, Mitochondrial; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D014810:Vitamin E; D013879:Thioredoxins; D024505:Tocopherols