Hexavalent chromium [Cr (VI)] is a well‐established carcinogen. Cr (VI)‐treated cells are phenotypically characterized by aberrant levels of growth and migration. Curcumin, a polyphenolic compound from the plant turmeric, has been found to possess antiproliferation, anti‐inflammation, and antioxidant properties. In this study, the effect of curcumin on Cr (VI)‐induced cell survival and migration and the underlying mechanism were investigated. Cell viability assay on A549 and human embryonic lung fibroblast cells showed that curcumin at the concentration of 10 µM could significantly attenuate Cr (VI)‐induced viability in both cell lines. Following Western blot assay and metabolomics assays, cotreatment with curcumin and Cr (VI) resulted in the suppression of Cr (VI)‐induced glycolysis‐, autophagy‐, and migration‐related proteins. Meanwhile, curcumin increased Cr (VI)‐reduced oxidative phosphorylation (OXPHOS)‐related proteins, COXIV and ND1. Moreover, curcumin suppressed Cr (VI)‐induced mitochondrial dysfunction, mitochondrial mass decrease, and mitochondrial membrane potential loss. Treatment with curcumin for 24 h significantly attenuated pcATG4B‐induced autophagy and the subsequent expression of glucose transporter 1, hexokinase II, and pyruvate kinase M2. Wound healing and transwell assay demonstrated that curcumin reduced Cr (VI)‐induced cell migration. Taken together, these results showed that curcumin was able to attenuate Cr (VI)‐induced cell viability and migration by targeting autophagy‐dependent reprogrammed metabolism from OXPHOS to glycolysis.

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