2. Academic Validation
  3. Butyrate enhances erastin-induced ferroptosis of osteosarcoma cells via regulating ATF3/SLC7A11 pathway

Butyrate enhances erastin-induced ferroptosis of osteosarcoma cells via regulating ATF3/SLC7A11 pathway

  • Eur J Pharmacol. 2023 Aug 22;176009. doi: 10.1016/j.ejphar.2023.176009.
Jiangbo Nie 1,  Yuhang Ling 2,  Mingchao Jin 1,  Zhuo Chen 1,  Wei Liu 3,  Weiyun Shen 2,  Tianshun Fang 1,  Jianyou Li 4,  Ying He 5
Affiliations

Affiliations

  • 1 Department of Orthopedics, Huzhou Central Hospital, Huzhou, Zhejiang, 313000, China; Zhejiang University Huzhou Hospital, Huzhou, Zhejiang, 313000, China.
  • 2 Central Laboratory, The First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, 313000, China; Huzhou Key Laboratory of Translational Medicine, The First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, 313000, China.
  • 3 Department of Orthopedics, Huzhou Central Hospital, Huzhou, Zhejiang, 313000, China.
  • 4 Department of Orthopedics, Huzhou Central Hospital, Huzhou, Zhejiang, 313000, China; Zhejiang University Huzhou Hospital, Huzhou, Zhejiang, 313000, China. Electronic address: ljywn1977@126.com.
  • 5 Central Laboratory, The First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, 313000, China; Huzhou Key Laboratory of Translational Medicine, The First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, 313000, China. Electronic address: 51578@zjhu.edu.cn.
PMID: 37619784 DOI: 10.1016/j.ejphar.2023.176009
Abstract

Osteosarcoma (OS) is a highly fatal bone tumor characterized by high degree of malignancy and early lung metastasis. Traditional chemotherapy fails in improving the efficacy and survival rate of patients with OS. Butyrate (NaBu) has been reported as a new antitumor drug for inhibiting proliferation and inducing Apoptosis in various Cancer cells. However, the effect of NaBu on the Ferroptosis of osteosarcoma is still unknown. This study aimed to investigate whether NaBu promotes erastin-induced Ferroptosis in OS cells and to uncover the underlying mechanism. Here, we found that NaBu significantly enhanced erastin-induced Ferroptosis in vitro. Compared with the group that erastin used alonely, pre-treating with NaBu exacerbated erastin-meditated GSH depletion, lipid peroxidation, and mitochondrial morphologic changes in OS cells. In a subcutaneous OS model, NaBu combined with erastin significantly reduced tumor growth and increased the levels of 4-HNE. Mechanistically, NaBu downregulated SLC7A11 transcription via regulating ATF3 expression. Overexpression of ATF3 facilitated erastin to induce Ferroptosis, while ATF3 knockdown attenuated NaBu-induced Ferroptosis sensitivity. In conclusion, our findings revealed a previously unidentified role of NaBu in erastin-induced Ferroptosis by regulating SLC7A11, suggesting that NaBu may be a potential therapeutic agent for OS treatment.

Keywords

ATF3; Butyrate; Ferroptosis; Osteosarcoma; SLC7A11.

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