The Curcuminoid EF24 in Combination with TRAIL Reduces Human Renal Cancer Cell Migration by Decreasing MMP-2/MMP-9 Activity through a Reduction in H2O2

Abstract

Cancer cells present high levels of oxidative stress, and although an increase in reactive oxygen species (ROS), such as H2O2, can lead to apoptosis, it can also induce cell invasion and metastasis. As the increase in ROS can lead to an increase in the expression of MMP-2 and MMP-9, thus causing the degradation of the extracellular matrix, an increase in the ROS H2O2 might have an impact on MMP-2/MMP-9 activity. The natural compound curcumin has shown some anticancer effects, although its bioavailability hinders its therapeutic potential. However, curcumin and its analogues were shown to resensitize kidney cancer cells to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. This study shows that the curcuminoid EF24 in combination with TRAIL increases peroxidase activity in the renal adenocarcinoma cell line ACHN, reducing the level of intracellular H2O2 and MMP-2/MMP-9 activity, a mechanism that is also observed after treatment with curcumin and TRAIL.