Curcumin activates the JNK signaling pathway to promote ferroptosis in colon cancer cells

Abstract Recent evidence has proved that curcumin as a natural polyphenol have a great anticancer and anti‐proliferative effects in cancer cells. Ferroptosis, a new form of regulated cell death, plays a vital role in the pathogenesis and therapy of cancers. In this study, we aimed to examine the effects of curcumin in ferroptosis of human colorectal cancer cells and its underlying molecular mechanisms. SW‐480 colorectal cancer cells were treated by curcumin with different concentrations. Cell viability was determined by using MTT assay. The concentrations of reactive oxygen species (ROS) and intracellular iron were measured using specific related kits. Real‐time PCR and Western blot analysis were used to determine the expression of ferroptosis‐related proteins including ACSL4, GPx4 and FTH1 and activation of JNK protein. Curcumin suppressed SW‐480 cancer cells viability in dose‐dependent manner. Cell treatment with curcumin led to accumulation of ROS and iron within cells and increase in the intracellular levels of lipid peroxidation. In addition, curcumin modulated the mRNA and protein expression levels of ferroptosis‐related proteins including ACSL4, GPx4 and FTH1 and suppression of JNK signaling. Curcumin may exhibit its anticancer effect on colorectal cancer by downregulating JNK signaling to induce ferroptosis in SW‐480 cells.