Curcumin Induces Ferroptosis in Colorectal Cancer SW620 Cells by Regulating SLC7A11/GSH/GPX4 Signaling Axis
Objective:To decipher the mechanism of curcumin in inhibiting the proliferation and inducing the ferroptosis of human colorectal cancer SW620 cells by regulating the solute carrier family 7 member 11(SLC7A11)/glutathione(GSH)/glutathione peroxidase 4(GPX4)signa-ling axis.Methods:The methyl thiazolyl tetrazolium(MTT)method was used to examine the effect of curcumin on the proliferation of SW620 cells.The effect of curcumin on the colony formation of SW620 cells was assessed by the colony formation assay.The effect of curcumin on the ferroptosis in SW620 cells was observed by transmission electron microscopy.The effects of curcumin on the intracellular Fe2+and lipid peroxide levels of SW620 cells were detected by the fluorescent probe.The malondialdehyde(MDA)concentration and GSH/oxidized gluta-thione(GSSG)ratio in the SW620 cells treated with curcumin were measured by the kits.The mRNA and protein levels of ferroptosis-related factors in the SW620 cells treated with curcumin were determined by qRT-PCR and Western blotting,respectively.Results:Compared with the model control,curcumin inhibited the proliferation of SW620 cells.After treatment with curcumin at 20 μmol/L,the mitochondria of SW620 cells showed a typical morphology of ferroptosis.Curcumin increased the levels of MDA,Fe2+,and lipid peroxides and reduced the GSH/GSSG ratio in SW620 cells(P＜0.01),which suggested that curcumin induced ferroptosis in SW620 cells.Compared with the model control,curcumin at 20 μmol/L and 40 μmol/L up-regulated the mRNA and protein levels of p53(P＜0.01 or P＜0.05)and down-regulated the mRNA and protein levels of Slc7a11 and Gpx4(P＜0.01 or P＜0.05),thereby inducing ferroptosis in SW620 cells.Conclusion:Curcu-min has anti-colorectal cancer effects,and it induces ferroptosis in colorectal cancer cells by inhibiting the SLC7A11/GSH/GPX4 signaling axis.The findings provide experimental support for the clinical application of curcumin in treating cancer.
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