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. Freeman^a and Jiri Neuzil^{a, 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.

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.

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