Effect of Isothiocyanates on Nuclear Accumulation of NF-κB, Nrf2, and Thioredoxin in Caco-2 Cells

Abstract

Early effects (only 1 h of exposure) of three isothiocyanates (benzyl, phenylethyl, and sulforaphane) on nuclear accumulation of thioredoxin, APE/Ref-1, and transcription factors NF-κB and Nrf2, as well as production of reactive oxygen species (ROS) and reduced glutathione levels were examined in human adenocarcinoma Caco-2 cells. Nuclear increase of NF-κB, Nrf2, and thioredoxin contents was observed in all isothiocyanate-treated cells, whereas the nuclear Ref-1 and cytoplasmic Keap1 contents were not changed. Sulforaphane was the most potent inducer of Nrf2 nuclear accumulation (10 μM, 1.9-fold) and NF-κB nuclear accumulation at higher concentration (25 μM, 6.3-fold). In contrast, benzyl isothiocyanate induced more thioredoxin nuclear accumulation (10 μM, 2.9-fold), increased production of ROS, and gave the greatest induction of thioredoxin reductase 1 mRNA (10 μM, 10.2-fold), whereas phenylethyl isothiocyanate was more potent in the depletion of reduced glutathione levels. These results show that different individual isothiocyanates may possess some different activities in nuclear accumulation of thioredoxin, NF-κB, Nrf2, and production of ROS. Keywords: Isothiocyanate; NF-κB; Nrf2; thioredoxin; redox; nuclear translocation