Targeting thioredoxin reductase by eupalinilide B promotes apoptosis of colorectal cancer cells in vitro and in vivo

Aberrant activation of thioredoxin reductase (TrxR) is correlated with tumor occurrence and progression, suggesting that TrxR inhibitors can be used as antitumor agents. In this study, we evaluated the anticancer efficacy of eupalinilides B on colorectal cancer cells. Eupalinilides B primarily targeted the conserved selenocysteine 498 residues in TrxR. Besides, it inhibited the enzyme activity in an irreversible manner. After eupalinilides B was used to pharmacologically inhibit TrxR, reactive oxygen species accumulated, and the intracellular redox balance was broken, finally causing oxidative stress-induced tumor cell apoptosis. Significantly, eupalinilides B treatment inhibited in vivo tumor growth. Targeting TrxR by eupalinilides B reveals the new mechanism underlying eupalinilides B and provides insight in developing eupalinilides B as the candidate antitumor chemotherapeutic agent for the treatment of cancer. [Display omitted] •Eupalinilides B inhibits thioredoxin reductase in vitro and in RKO and HCT116 cells.•Eupalinilides B treatment leads to accumulation of ROS and depletion of cellular thiols.•Eupalinilides B induces oxidative stress-mediated apoptosis in RKO and HCT116 cells.•Eupalinilides B treatment leads to tumor growth inhibition in colorectal cancer RKO Xenograft.