Surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF-MS) as a tool for molecular endpoint analysis of PX-12, a thioredoxin-1 inhibitor

Abstract

Thioredoxin-1 is a redox protein upregulated in many cancers. Its functions include inhibition of apoptosis, increasing cellular growth and proliferation. It has been shown that cells displaying increased levels of Trx-1 have increased drug resistance. PX-12 is a Trx-1 inhibitor that shows anti-proloferative and cytotoxic activity in vitro and in vivo. We used surface enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF-MS) to measure plasma Trx-1 levels of patients treated with PX-12 as a side study of a phase-I trial. SELDI-TOF-MS was able to measure a decrease in plasma Trx-1 after PX-12 treatment semi-quantitatively. In addition, SELDI measured 57 other protein peaks in plasma; seven which were found in all plasma samples analyzed. One of these peaks was located at 13.86kDa and identified through LC-MS/MS sequencing to be a variant of Transthyretin. Further studies into these additional peaks are necessary to determine their biological importance in relation to Trx-1 and PX-12.