2. Academic Validation
  3. Ciclopirox drives growth arrest and autophagic cell death through STAT3 in gastric cancer cells

Ciclopirox drives growth arrest and autophagic cell death through STAT3 in gastric cancer cells

  • Cell Death Dis. 2022 Nov 28;13(11):1007. doi: 10.1038/s41419-022-05456-7.
Lingyan Chen # 1 2,  Dejian Chen # 1 2,  Jiwei Li 1 2,  Lipeng He 1 2,  Ting Chen 1 2,  Dandan Song 1 2,  Shuang Shan 1 2,  Jiaxin Wang 1 2,  Xiaoang Lu 1 2,  Bin Lu 3 4
Affiliations

Affiliations

  • 1 Protein Quality Control and Diseases Laboratory, Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
  • 2 The Affiliated Nanhua Hospital and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
  • 3 Protein Quality Control and Diseases Laboratory, Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. lubinmito@usc.edu.cn.
  • 4 The Affiliated Nanhua Hospital and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. lubinmito@usc.edu.cn.
  • # Contributed equally.
PMID: 36443287 DOI: 10.1038/s41419-022-05456-7
Abstract

Ciclopirox (CPX), an Antifungal drug, has recently been identified as a promising agent for Cancer treatment. However, the effects and underlying mechanism of CPX as an antitumor agent of gastric Cancer (GC) remain largely unknown. Here, we found that CPX dramatically suppresses GC xenograft growth in vitro via inhibiting proliferation and stimulating autophagic cell death rather than Apoptosis. Moreover, CPX (20 mg/kg, intraperitoneally) substantially inhibits GC xenograft tumor growth in vivo. Mechanistically, CPX promotes growth arrest and autophagic cell death through suppressing the phosphorylation of signal transducers and activators of transcription 3 (STAT3) at tyrosine 705 (Tyr705) and serine 727 (Ser727) sites, respectively. Additionally, CPX induces STAT3 ubiquitination, which subsequently leads to a decrease in the p-STAT3 (Ser727) level. On the other hand, CPX represses the p-STAT3 (Tyr705) level via p-Src (Tyr416) inhibition. Collectively, our findings unmask a novel mechanism by which CPX regulates growth and autophagic cell death in GC cells via regulating the phosphorylation of STAT3 both at Tyr705 and Ser727 residues, and suggest that CPX may be a potential treatment for GC.

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