Proteomics revealed the crosstalk between copper stress and cuproptosis, and explored the feasibility of curcumin as anticancer copper ionophore

Yang, Ying; Liang, Shuyu; Geng, Hongen; Xiong, Mengmeng; Li, Man; Su, Qian; Jia, Fang; Zhao, Yimei; Wang, Kai; Jiang, Jun; Qin, Si; Li, Xiang

doi:10.1016/j.freeradbiomed.2022.11.023

Cited by 30 publications

(16 citation statements)

References 51 publications

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“…These results confirm a significant decrease in mitochondrial acidity during ES-induced cuproptosis, which is accordant with the results reportorial in the literature. 17,18 Meanwhile, the green channel fluorescence intensity enhanced, indicating that the endogenous SO 2 concentration in HeLa cells boosted transiently with an increasing inducer concentration. However, there was a threshold for the increase in the SO 2 content.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…On the other hand, changes in the Cu 2+ concentration in living cells can cause fluctuations in the pH of the cells . Normal mitochondrial pH is known to be alkaline, and nevertheless, mitochondrial dysregulation during cuproptosis leads to abnormal ion influx, which may affect the pH of the mitochondrial matrix . Meanwhile, it has been indicated that the pH value of mitochondria shows a significant part in their physiological functions. − The normal cellular mitochondrial pH range is slightly alkalescent (pH ≈ 8.00) .…”

Section: Introductionmentioning

confidence: 99%

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Polysiloxane-Based Molecular Logic Gate for Dual-Channel Visualizing Mitochondrial pH and Sulphite Changes during Cuproptosis

Wang,

Lan,

Zuo

2023

Anal. Chem.

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Intracellular Cu-induced regulated cell death, characterized by the aggregation of lipidizing mitochondrial enzymes, is called cuproptosis. Mitochondria play a vital role in the metabolic regulation of cell injury and stressful immune responses. The pH levels and sulfur dioxide (SO 2 ) content in mitochondria have important indicative roles in the regulation of cuproptosis. However, fluorescent probes that simultaneously detect changes in pH and SO 2 in mitochondria during cuprotosis have not been reported. To fill this blank, in this study, we dexterously used functional polysiloxane as a fluorescent platform to propose a molecular logic gate probe P 0 -pH-SO 2 for detecting changes in intramitochondrial pH and SO 2 content through a dualchannel mode. In addition, we defined a new function to reflect the cellular state of the elesclomol-induced cuproptosis process based on the input and output of the relevant logic relationship. This new fluorescent molecular logic gate probe P 0 -pH-SO 2 can be rapidly activated by mitochondrial sulfites to induce green fluorescence, while the red fluorescence is quenched with the proton in the mitochondria. Overall, this study developed a novel logic-gated molecular probe that provided a versatile strategy for monitoring the role played by intramitochondrial sulfites and H + in cuproptosis. This work will open the way to broaden the applications of molecular logic gates and fluorescent polysiloxanes.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polysiloxane-Based Molecular Logic Gate for Dual-Channel Visualizing Mitochondrial pH and Sulphite Changes during Cuproptosis

Wang,

Lan,

Zuo

2023

Anal. Chem.

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“…Then, the labeled peptides were combined, desalted, and subjected to offline basic pH reversed-phase (bRP) fractionation as previously reported. 39,40 The fractionated peptides were then dived in SpeedVac and redissolved in 0.1% FA for LC-MS/MS.…”

Section: Proteomics Sample Preparationmentioning

confidence: 99%

Photochemically Controlled Release of the Glucose Transporter 1 Inhibitor for Glucose Deprivation Responses and Cancer Suppression Research

Geng,

Chen,

et al. 2024

J. Proteome Res.

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Cancer cells need a greater supply of glucose mainly due to their aerobic glycolysis, known as the Warburg effect. Glucose transport by glucose transporter 1 (GLUT1) is the ratelimiting step for glucose uptake, making it a potential cancer therapeutic target. However, GLUT1 is widely expressed and performs crucial functions in a variety of cells, and its indiscriminate inhibition will cause serious side effects. In this study, we designed and synthesized a photocaged GLUT1 inhibitor WZB117-PPG to suppress the growth of cancer cells in a spatiotemporally controllable manner. WZB117-PPG exhibited remarkable photolysis efficiency and substantial cytotoxicity toward cancer cells under visible light illumination with minimal side effects, ensuring its safety as a potential cancer therapy. Furthermore, our quantitative proteomics data delineated a comprehensive portrait of responses in cancer cells under glucose deprivation, underlining the mechanism of cell death via necrosis rather than apoptosis. We reason that our study provides a potentially reliable cancer treatment strategy and can be used as a spatiotemporally controllable trigger for studying nutrient deprivation-related stress responses.

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“…1 A), a bioactive dietary polyphenol of turmeric [ 12 ], has a broad range of biological functions [ 13 , 14 ]. Several studies have demonstrated the protective effects of Cur against varied cancers, including lung cancer, breast cancer, gastric cancer, CRC and so on [ 15 , 16 ]. In addition, an epidemiological analysis showed an association between dietary consumption of Cur and decreased incidence of CRC in the Indian population [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Curcumin suppresses cell proliferation and reduces cholesterol absorption in Caco-2 cells by activating the TRPA1 channel

Qin

et al. 2023

Lipids Health Dis

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Background Curcumin (Cur) is a bioactive dietary polyphenol of turmeric with various biological activities against several cancers. Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths. Intestinal cholesterol homeostasis is associated with CRC. Chemotherapy for CRC is related to varied adverse effects. Therefore, natural products with anti-cancer properties represent a potential strategy for primary prevention of CRC. Methods The present study used Cur as a therapeutic approach against CRC using the Caco-2 cell line. The cells were treated with different concentrations of Cur for different duration of time and then the proliferation ability of cells was assessed using Cell Counting Kit-8 and 5-Ethynyl-2′-deoxyuridine assays. Oil red O staining and cholesterol assay kit were used to evaluate cellular lipid content and cholesterol outward transportation. Finally, the protein expressions of cholesterol transport-related protein and signal transduction molecules were assessed using Western blot assay. Results Cur inhibited cell proliferation in Caco-2 cells in a dose- and time-dependent manner by activating the transient receptor potential cation channel subfamily A member 1 (TRPA1) channel. Activation of the TRPA1 channel led to increased intracellular calcium, peroxisome proliferator-activated receptor gamma (PPARγ) upregulation, and the subsequent downregulation of the specificity protein-1 (SP-1)/sterol regulatory element-binding protein-2 (SREBP-2)/Niemann-Pick C1-like 1 (NPC1L1) signaling pathway-related proteins, and finally reduced cholesterol absorption in Caco-2 cells. Conclusions Cur inhibits cell proliferation and reduces cholesterol absorption in Caco-2 cells through the Ca2+/PPARγ/SP-1/SREBP-2/NPC1L1 signaling by activating the TRPA1 channel, suggesting that Cur can be used as a dietary supplement for the primary prevention of CRC. Graphical Abstract In Caco-2 cells, Cur first stimulates calcium influx by activating the TRPA1 channel, further upregulates PPARγ and downregulates SP-1/SREBP-2/NPC1L1 signaling pathway, and finally inhibits the absorption of cholesterol. TRPA1, transient receptor potential cation channel subfamily A member 1; NPC1L1, Niemann-Pick C1-like 1; PPARγ, peroxisome proliferator-activated receptor gamma; SP-1, specificity protein-1; SREBP-2, sterol regulatory element-binding protein-2; Cur, curcumin.

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Proteomics revealed the crosstalk between copper stress and cuproptosis, and explored the feasibility of curcumin as anticancer copper ionophore

Cited by 30 publications

References 51 publications

Polysiloxane-Based Molecular Logic Gate for Dual-Channel Visualizing Mitochondrial pH and Sulphite Changes during Cuproptosis

Polysiloxane-Based Molecular Logic Gate for Dual-Channel Visualizing Mitochondrial pH and Sulphite Changes during Cuproptosis

Photochemically Controlled Release of the Glucose Transporter 1 Inhibitor for Glucose Deprivation Responses and Cancer Suppression Research

Curcumin suppresses cell proliferation and reduces cholesterol absorption in Caco-2 cells by activating the TRPA1 channel

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