Deferasirox induces cyclin D1 degradation and apoptosis in mantle cell lymphoma in a reactive oxygen species? and GSK3??dependent mechanism

Mantle cell lymphoma (MCL) is a difficult-to-treat B-cell malignancy characterized by cyclin D1 (CD1) overexpression. Targeting CD1 in MCL has been shown to be of therapeutic significance. However, treatment remains challenging since patients are still subject early and frequent relapse the disease. To ensure their high proliferation rate, tumour cells have increased iron needs, making them more susceptible deprivation. Indeed, several chelators proved effective anti-cancer agents. In this study, we demonstrate that clinically approved chelator deferasirox (DFX) exerts an anti-tumoural effect lines patient cells. The exposure feasible concentrations DFX resulted growth inhibition, cycle arrest induction apoptosis. We show unfolds its cytotoxic rapid reactive oxygen species (ROS) leads oxidative stress severe DNA damage triggering proteolysis mechanism requires phosphorylation on T286 glycogen synthase kinase-3? (GSK3?). Moreover, mediates repressing phosphatidylinositol 3-kinase (PI3K)/AKT/GSK3? pathway via ROS generation. Our data suggest as potential option for paves way options these patients.