Role of thioredoxin-1 in apoptosis induction by α-tocopheryl succinate and TNF-related apoptosis-inducing ligand in mesothelioma cells

FEBS Letters. 2006 May 15;580(11):2671-6. Epub 2006 Apr 21. [Link]

Ruth E. Freemana and Jiri Neuzila, b

aApoptosis Research Group, Heart Foundation Research Centre, School of Medical Science, Griffith University, Southport, Qld 9716, Australia
bLaboratory of Cell Signalling and Apoptosis, Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic

Received 28 December 2005;  revised 23 March 2006;  accepted 5 April 2006.  Available online 21 April 2006.


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.

Keywords: Apoptosis; Malignant mesothelioma; Thioredoxin-1; α-Tocopheryl succinate; TNF-related apoptosis-inducing ligand

Abbreviations: ELISA, enzyme-linked immuno-sorbent assay; FCS, fetal calf serum; MM, malignant mesothelioma; Q-PCR, quantitative reversed-transcription PCR; ROS, reactive oxygen species; siRNA, short interfering RNA; α-TOS, α-tocopheryl succinate; TRAIL, TNF-related apoptosis-inducing ligand; Trx-1, thioredoxin-1