2. Academic Validation
  3. Thiostrepton induces oxidative stress, mitochondrial dysfunction and ferroptosis in HaCaT cells

Thiostrepton induces oxidative stress, mitochondrial dysfunction and ferroptosis in HaCaT cells

  • Cell Signal. 2024 Sep:121:111285. doi: 10.1016/j.cellsig.2024.111285.
MeiYu Chen 1,  QiXia Wang 2,  YaoQun Wang 1,  Yuan Xuan 1,  MengYuan Shen 1,  XiaoPing Hu 1,  YunJin Li 3,  Yi Guo 4,  Juan Wang 5,  Fei Tan 6
Affiliations

Affiliations

  • 1 Shanghai Skin Disease Clinical College, The Fifth Clinical Medical College, Anhui Medical University, Shanghai Skin Disease Hospital, Shanghai 200443, People's Republic of China.
  • 2 Department of General Practice, Xi'an Central Hospital, Xi'an, Shaanxi 710000, China.
  • 3 Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200443, China.
  • 4 SICU, Fuwai Yunnan Hospital, Chinese Academy of Medical Sciences, Kunming, Yunnan 650102, China.
  • 5 Department of Ophthalmology of Shanghai Tongji Hospital, Laboratory of Clinical Visual Science of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, China; Department of Medical Genetics, School of Medicine, Tongji University, Shanghai, China. Electronic address: juanwang@tongji.edu.cn.
  • 6 Shanghai Skin Disease Clinical College, The Fifth Clinical Medical College, Anhui Medical University, Shanghai Skin Disease Hospital, Shanghai 200443, People's Republic of China; Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200443, China. Electronic address: tanfeitrue@126.com.
PMID: 38969192 DOI: 10.1016/j.cellsig.2024.111285
Abstract

TST has been mainly studied for its anti-tumor proliferation and antimicrobial effects, but not widely used in dermatological diseases. The mechanism of cellular damage by TST in response to H2O2-mediated oxidative stress was investigated in human skin immortalized keratinocytes (HaCaT) as an in vitro model. The findings reveal that TST treatment leads to increased oxidative stress in the cells by reducing levels of superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT). This effect is further supported by an upsurge in the expression of malondialdehyde (MDA, a pivotal marker of lipid peroxidation). Additionally, dysregulation of FoxM1 at both gene and protein levels corroborates its involvement TST associated effects. Analysis of ferroptosis-related genes confirms dysregulation following TST treatment in HaCaT cells. Furthermore, TST treatment exhibits effects on mitochondrial morphology and function, affirming its induction of Apoptosis in the cells through heightened oxidative stress due to mitochondrial damage and dysregulation of mitochondrial membrane potential.

Keywords

Ferroptosis; FoxM1; Mitochondria dysfunction; Oxidative stress; Thiostrepton.

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