Role of thioredoxin-1 in apoptosis induction by α-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 α-tocopheryl succinate (α-TOS) and TNF-related apoptosis-inducing ligand (TRAIL). MM cells were susceptible to α-TOS and less to TRAIL, while Met-5A cells were susceptible to TRAIL and resistant to α-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 α-TOS. Our data suggest that the role of Trx-1 in apoptosis modulation is unrelated to its anti-oxidant properties.