Curcumin attenuates Cr (VI)‐induced cell growth and migration by targeting autophagy‐dependent reprogrammed metabolism

Abstract

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.

Autophagy Activation Promoted by Pulses of Light and Phytochemicals Counteracting Oxidative Stress during Age-Related Macular Degeneration

“…These results suggest a very promising protective effect of curcumin in the course of AMD. In fact, the autophagy-inducing properties of curcumin in various cell types are magnificent compared with other phytochemicals [59,145,146,[155][156][157][158][159], and they are similar to those reported for rapamycin [144,[160][161][162][163][164][165] with the important difference that curcumin does not carry the burden of most side effects induced by rapamycin. The protective effects of curcumin in restoring autophagy in the RPE are comparable to those described for lutein [113].…”

“…In fact, this compound stimulates autophagy both in baseline conditions and following toxic stimuli. The protective effects of curcumin are demonstrated in various cell types, where curcumin acts as an autophagy inducer [ 120 , 141 , 142 , 143 , 144 , 145 , 146 , 147 ]. When looking at retinal site-specific effects, curcumin counteracts apoptosis and inhibits MAPK-dependent signaling in experimental retinal degeneration [ 148 , 149 ].…”

The Essential Role of Light-Induced Autophagy in the Inner Choroid/Outer Retinal Neurovascular Unit in Baseline Conditions and Degeneration

“…The seminal role of autophagy in sustaining retinal integrity during AMD is likely to be naturally induced by long wave-length light pulses and light-sensitive phytochemicals, which are reported to maintain retinal structure and visual acuity, as well as to counteract retinal degeneration [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. In contrast, short wave-length light and metabolic dysfunctions may induce deleterious effects by altering a number of chemical species, which undergo conformational changes, deranging a number of organelles, which are affected during the high metabolic turn-over of this part of the retina.…”

Curcumin, its derivatives, and their nanoformulations: Revolutionizing cancer treatment

“…24,34 Moreover, curcumin prevents glucose uptake and lactate production in cancer cells by inhibiting pyruvate kinase M2 through downregulation of the mammalian target of rapamycin (mTOR)-hypoxia-inducible factor 1. [35][36][37]…”

“…Curcumin and its derivatives also have a potent ability to induce apoptosis in a variety of cell lines via the suppression of intracellular transcription factors, such as nitric oxide synthase, signal transducer and activator transcription 3 (STAT3), and matrix metalloproteinase‐9 (MMP‐9) 24,34 . Moreover, curcumin prevents glucose uptake and lactate production in cancer cells by inhibiting pyruvate kinase M2 through downregulation of the mammalian target of rapamycin (mTOR)‐hypoxia‐inducible factor 1 35–37 …”