The combination of digoxin and GSK2606414 exerts synergistic anticancer activity against leukemia in vitro and in vivo.

Digoxin is a member of cardiac glycosides and recent studies show that digoxin plays anticancer role in several types of cancer. However, the anticancer effects and mechanism of digoxin in leukemia is largely unknown. Her, our data show that digoxin treatment significantly inhibits leukemia cell viability. In addition, digoxin treatment significantly induced apoptosis and G2/M cell cycle arrest in leukemia cells. Furthermore, we demonstrated that digoxin treatment inactivate that oncogenic pathway Akt/mTOR signaling in leukemia cells. In addition, our data show that digoxin treatment induces activation of unfolded protein response (UPR) signaling in leukemia cells. Interestingly, our in vitro and in vivo experiments show that combination treatment of digoxin and UPR inhibitor can synergistically suppress leukemia growth and induces apoptosis and cell cycle arrest compared to single drug treatment. In summary, our findings indicate that digoxin has potential anticancer effects on leukemia. The combination of digoxin and UPR signaling inhibitor can exerts synergistic anticancer activity against leukemia.