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Keywords {🔍}

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Topics {✒️}

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Questions {❓}

• Understanding Metal Dynamics between Cancer cells and macrophages: competition or synergism?

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WebPage:
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         headline:Ferroptosis inducers enhanced cuproptosis induced by copper ionophores in primary liver cancer
         description:Cuproptosis and ferroptosis are the two newly defined metal-related regulated cell death. However, the crosstalk between cuproptosis and ferroptosis is obscure. We analyzed the effect of ferroptosis inducers on copper ionophores-induced cell death through CCK-8 assay. Cuproptosis was studied using immunofluorescence and protein soluble-insoluble fraction isolation. GSH assay, qRT-PCR and western blot were adopted to explore the machinery of ferroptosis inducers enhanced cuproptosis. And mouse xenograft model was built to detect the synergy effect of elesclomol-Cu and sorafenib in vivo. Herein we found that ferroptosis inducers sorafenib and erastin could enhance cuproptosis in primary liver cancer cells by increasing copper dependent lipoylated protein aggregation. Mechanically, sorafenib and erastin upregulated protein lipoylation via suppressing mitochondrial matrix-related proteases mediated ferredoxin 1 (FDX1) protein degradation, and reduced intracellular copper chelator glutathione (GSH) synthesis through inhibiting cystine importing. Our findings proposed that combination of ferroptosis inducers and copper ionophores to co-targeting ferroptosis and cuproptosis could be a novel therapeutic strategy for primary liver cancer.
         datePublished:2023-06-06T00:00:00Z
         dateModified:2023-06-06T00:00:00Z
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            Ferroptosis
            Copper ionophores
            Lipoylation
            Ferredoxin 1 (FDX1)
            Cancer Research
            Immunology
            Apoptosis
            Oncology
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                     address:
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      headline:Ferroptosis inducers enhanced cuproptosis induced by copper ionophores in primary liver cancer
      description:Cuproptosis and ferroptosis are the two newly defined metal-related regulated cell death. However, the crosstalk between cuproptosis and ferroptosis is obscure. We analyzed the effect of ferroptosis inducers on copper ionophores-induced cell death through CCK-8 assay. Cuproptosis was studied using immunofluorescence and protein soluble-insoluble fraction isolation. GSH assay, qRT-PCR and western blot were adopted to explore the machinery of ferroptosis inducers enhanced cuproptosis. And mouse xenograft model was built to detect the synergy effect of elesclomol-Cu and sorafenib in vivo. Herein we found that ferroptosis inducers sorafenib and erastin could enhance cuproptosis in primary liver cancer cells by increasing copper dependent lipoylated protein aggregation. Mechanically, sorafenib and erastin upregulated protein lipoylation via suppressing mitochondrial matrix-related proteases mediated ferredoxin 1 (FDX1) protein degradation, and reduced intracellular copper chelator glutathione (GSH) synthesis through inhibiting cystine importing. Our findings proposed that combination of ferroptosis inducers and copper ionophores to co-targeting ferroptosis and cuproptosis could be a novel therapeutic strategy for primary liver cancer.
      datePublished:2023-06-06T00:00:00Z
      dateModified:2023-06-06T00:00:00Z
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         Cuproptosis
         Ferroptosis
         Copper ionophores
         Lipoylation
         Ferredoxin 1 (FDX1)
         Cancer Research
         Immunology
         Apoptosis
         Oncology
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      name:Laboratory of Cancer Biology, Key Lab of Biotherapy in Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Cancer Center of Zhejiang University, Zhejiang University, Hangzhou, China
      name:Laboratory of Cancer Biology, Key Lab of Biotherapy in Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Cancer Center of Zhejiang University, Zhejiang University, Hangzhou, China
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      name:Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
      name:Laboratory of Cancer Biology, Key Lab of Biotherapy in Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Cancer Center of Zhejiang University, Zhejiang University, Hangzhou, China
      name:Laboratory of Cancer Biology, Key Lab of Biotherapy in Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Cancer Center of Zhejiang University, Zhejiang University, Hangzhou, China

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