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Title:
Curcumin promotes ferroptosis in hepatocellular carcinoma via upregulation of ACSL4 | Journal of Cancer Research and Clinical Oncology
Description:
Background Ferroptosis, a novel iron-ion-dependent metabolic cell death mode with lipid peroxides as the main driving substrate, plays an irreplaceable role in the development and preventive treatment of hepatocellular carcinoma. Curcumin has potent pharmacological anti-tumor effects. Aim of the study We aimed to evaluate the ex vivo and in vivo cancer inhibitory activity of curcumin and its specific mechanism of action. Materials and Methods We used the hepatocellular carcinoma cell lines HepG2 and SMMC7721 to assess the direct inhibition of hepatocellular carcinoma proliferation by curcumin in vitro and a tumor xenograft model to evaluate the in vivo cancer inhibitory effect of curcumin. Results In this study, we found that ferroptosis’s inhibitors specifically reversed the curcumin-induced cell death pattern in HCC. After curcumin intervention, there was a substantial increase in MDA levels and iron ion levels, and a decrease in intracellular GSH levels. Meanwhile, the expression of GPX4 and SLC7A11 was significantly reduced at the protein levels, while ACSL4 and PTGS2 expression was significantly increased. Conclusions This study showed that curcumin significantly decreased the proliferation of HCC cells and significantly increased the sensitivity of ferroptosis. These results suggest that ACSL4 is a viable target for curcumin-induced ferroptosis in treating HCC.
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Keywords {🔍}
curcumin, cells, ferroptosis, cell, acsl, hepatocellular, carcinoma, hcc, pubmed, article, levels, fig, cancer, google, scholar, hepg, assay, significantly, expression, liver, death, increased, cas, central, tumor, treatment, proliferation, effect, intracellular, chinese, lipid, mda, target, level, found, gsh, traditional, viability, mice, results, knockdown, smmc, protein, plate, tissues, medicine, study, increase, showed, shanghai,
Topics {✒️}
activate ros/keap1/nrf2/mir-34a/ ros/keap1/nrf2/mir-34a/ pi3k/akt/gsk-3beta signaling pi3k/akt/gsk-3β signaling pi3k/akt/gsk-3β pathway ros-yap-jnk signaling pathway il-1β/nf-κb pathways modulating mir-21–5p/sox6 axis aa-coa generates pufa-looh apoptosis inhibitor z-vad-fmk ros-yap-jnk pathway jak/stat3 signaling pathway mito-tracker red cmxros mitophagy-related gene signature article download pdf long-term proliferative capacity anti-programmed cell death-1 regulating il-6/jak/stat3 dose-dependent cytotoxic effect iron-death-related diseases inhibit long-term proliferation hrp-labeled secondary antibody anti-cancer chinese medicines cystine transporter slc7a11/xct curcumin-induced cell death ferroptosis-related lipid metabolism curcumin-enhanced antitumor effects dose-dependently increase cellular degradation systems inhibits hepatocellular carcinoma curcumin-mediated cell death z-vad-fmk calcein/pi assay staining autophagy-induced ferroptosis response dose-dependent manner cell death modalities programmed cell death privacy choices/manage cookies previous article reporting regulating mir-21-5p turn effectively inhibits iron ion dependence iron ion levels ferroptosis-related proteins slc7a11 mitochondrial membrane potential iron ion metabolism tumor growth curves shuguang hospital affiliated nf-κb activity triggered mitochondrial apoptosis
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headline:Curcumin promotes ferroptosis in hepatocellular carcinoma via upregulation of ACSL4
description:Ferroptosis, a novel iron-ion-dependent metabolic cell death mode with lipid peroxides as the main driving substrate, plays an irreplaceable role in the development and preventive treatment of hepatocellular carcinoma. Curcumin has potent pharmacological anti-tumor effects. We aimed to evaluate the ex vivo and in vivo cancer inhibitory activity of curcumin and its specific mechanism of action. We used the hepatocellular carcinoma cell lines HepG2 and SMMC7721 to assess the direct inhibition of hepatocellular carcinoma proliferation by curcumin in vitro and a tumor xenograft model to evaluate the in vivo cancer inhibitory effect of curcumin. In this study, we found that ferroptosis’s inhibitors specifically reversed the curcumin-induced cell death pattern in HCC. After curcumin intervention, there was a substantial increase in MDA levels and iron ion levels, and a decrease in intracellular GSH levels. Meanwhile, the expression of GPX4 and SLC7A11 was significantly reduced at the protein levels, while ACSL4 and PTGS2 expression was significantly increased. This study showed that curcumin significantly decreased the proliferation of HCC cells and significantly increased the sensitivity of ferroptosis. These results suggest that ACSL4 is a viable target for curcumin-induced ferroptosis in treating HCC.
datePublished:2024-09-23T00:00:00Z
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name:Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
type:PostalAddress
type:Organization
name:Xiaofan Yu
affiliation:
name:Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
address:
name:Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
type:PostalAddress
type:Organization
name:Shanghai University of Traditional Chinese Medicine
address:
name:Shanghai University of Traditional Chinese Medicine, Shanghai, China
type:PostalAddress
type:Organization
name:Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
address:
name:Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
type:PostalAddress
type:Organization
name:Chao Wu
affiliation:
name:Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
address:
name:Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
type:PostalAddress
type:Organization
name:Shanghai University of Traditional Chinese Medicine
address:
name:Shanghai University of Traditional Chinese Medicine, Shanghai, China
type:PostalAddress
type:Organization
name:Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
address:
name:Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
type:PostalAddress
type:Organization
name:Mingyu Sun
affiliation:
name:Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
address:
name:Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
type:PostalAddress
type:Organization
name:Shanghai University of Traditional Chinese Medicine
address:
name:Shanghai University of Traditional Chinese Medicine, Shanghai, China
type:PostalAddress
type:Organization
name:Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
address:
name:Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Shanghai University of Traditional Chinese Medicine, Shanghai, China
name:Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
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