1. Academic Validation
  2. Curcumin promotes ferroptosis in hepatocellular carcinoma via upregulation of ACSL4

Curcumin promotes ferroptosis in hepatocellular carcinoma via upregulation of ACSL4

  • J Cancer Res Clin Oncol. 2024 Sep 23;150(9):429. doi: 10.1007/s00432-024-05878-0.
Yulang Jiang # 1 2 3 Dengcheng Hui # 1 2 3 Ziyang Pan 1 2 3 Yongxin Yu 1 2 3 Lu Liu 1 2 3 Xiaofan Yu 1 2 3 Chao Wu 1 2 3 Mingyu Sun 4 5 6
Affiliations

Affiliations

  • 1 Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 2 Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 3 Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No.528 Zhangheng Road, Zhangjiang Hi-Tech Park, Shanghai, 201203, China.
  • 4 Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. mingyusun@shutcm.edu.cn.
  • 5 Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. mingyusun@shutcm.edu.cn.
  • 6 Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No.528 Zhangheng Road, Zhangjiang Hi-Tech Park, Shanghai, 201203, China. mingyusun@shutcm.edu.cn.
  • # Contributed equally.
Abstract

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.

Keywords

ACSL44; Curcumin1; Ferroptosis2; Hepatocellular carcinoma 3; Lipid peroxidation5.

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