Resveratrol induces ferroptosis in colorectal cancer SW480 cells and its mechanism

ObjectiveTo study the activation of ferroptosis by resveratrol in colorectal cancer SW480 cells, and to explore its possible mechanism.

MethodsAfter intervening SW480 cells with different doses of resveratrol(0, 10, 20, 40, 80, 160 μmol/L) for 24, 48 and 72 h, the effect of resveratrol on cell proliferation inhibition rate was analyzed by CCK8 method.After intervening SW480 cells with different doses of resveratrol(0, 20, 40, 80 μmol/L) for 48 h, Western blotting was used to analyze the expression levels of cystine/glutamate antiporter system Xc(xCT), glutathione peroxidase 4(GPX4) and divalent metal transporter 1(DMT1), and flow cytometry was applied to detect the change of reactive oxygen specie(ROS) level which was indicated by fluorescence intensity.

ResultsAfter SW480 cells were treated with resveratrol, the inhibition rate of cell proliferation was significantly increased, which showed a time- and concentr ation-dependent manner(P < 0.05);the expression level of xCT and GPX4 protein were significantly decreased, and the expression level of DMT1 was greatly increased(P < 0.05);resveratrol also induced the accumulation of ROS in SW480 cells(P < 0.05).

ConclusionsResveratrol increases the accumulation of ROS by inhibiting the expression of GPX4 and xCT protein to induce ferroptosis in SW480 cells, which may involve the activation of DMT1 expression.