4.7 Article

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

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Publisher

MDPI
DOI: 10.3390/ijms24021043

Keywords

curcumin; DMC; EF24; H2O2; kidney cancer; MMP; ROS; TRAIL

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Cancer cells have high levels of oxidative stress, and an increase in reactive oxygen species (ROS) can lead to both apoptosis and cell invasion. This can be attributed to the impact on MMP-2/MMP-9 activity caused by the increase in ROS H2O2, which degrades the extracellular matrix. Curcumin, although limited in bioavailability, has shown anticancer effects and can sensitize kidney cancer cells to TRAIL-induced apoptosis. This study demonstrates that the curcuminoid EF24, in combination with TRAIL, reduces intracellular H2O2 and MMP-2/MMP-9 activity in the renal adenocarcinoma cell line ACHN by increasing peroxidase activity.
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.

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