URI prevents potassium dichromate-induced oxidative stress and cell death in gastric cancer cells.

ABSTRACT

Chromium VI can provoke oxidative stress, DNA damage, cytotoxicity, mutagenesis and carcinogenesis. Aberrantly high level of reactive oxygen species (ROS) has been associated with oxidative stress and subsequent DNA damage. Notably, multiple previous studies have shown the increased level of ROS in chromium (VI) induced oxidative stress, but its effect on cell death and the underlying mechanism remain to be determined. In this study, we aimed to investigate the role of URI, an unconventional prefoldin RBP5 interactor, in potassium dichromate induced oxidative stress and cell death through in vitro loss-of-function studies. We have shown that knockdown of URI in human gastric cancer SGC-7901 cells by URI siRNA enhanced potassium dichromate-induced production of ROS. The level of rH2AX, a marker of DNA damage, was significantly increased, along with a reduced cell viability in URI siRNA treated cells that were also exposed to potassium dichromate. Comet assay showed that URI knockdown increased the tail moment in potassium dichromate-treated SGC-7901 cells. Accordingly, the cell rates of apoptosis and necrosis were also increased in URI knockdown cells treated with potassium dichromate at different concentrations. Together, these results suggest that URI is preventive for the oxidative stress and cell death induced by potassium dichromate, which potentially leads to cancer cell survival and therapeutic resistance.