Thiostrepton suppresses triple-negative breast cancer through downregulating c-FLIP/SMAD2/3 signaling pathway

  • J Asian Nat Prod Res. 2024 Apr 18:1-10. doi: 10.1080/10286020.2024.2343420.
Wen-Die Wang  1 ,  Chao-Yang Zeng  1 ,  Yue Shang  1 ,  Jun Ni  1 ,  Gao-Jie Li  1 ,  Li-Ping Li  1 ,  Shuo-Han Xi  1 ,  Shu-Zhen Chen  1  2
Affiliations
  • 1. Department of Cancer Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China.
  • 2. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.
PMID: 38634704 DOI: 10.1080/10286020.2024.2343420
Abstract

Triple-negative breast Cancer (TNBC) is an aggressive subtype with poor prognosis of breast Cancer. Thiostrepton exerts anti-tumor activities against several cancers including TNBC. Herein we discussed the new molecular mechanisms of thiostrepton in TNBC. Thiostrepton inhibited MDA-MB-231 cell viability, accompanied by a decrease of c-FLIP and p-SMAD2/3. c-FLIP overexpression reduced the sensitivity of MDA-MB-231 cells to thiostrepton, while SMAD2/3 knockdown increased the sensitivity of MDA-MB-231 cells to thiostrepton. Moreover, c-FLIP overexpression significantly increased the expression and phosphorylation of SMAD2/3 proteins and vice versa. In conclusion, our study reveals c-FLIP/SMAD2/3 signaling pathway as a novel mechanism of antitumor activity of thiostrepton.

Keywords
SMAD2/3; Thiostrepton; c-FLIP; triple-negative breast cancer (TNBC).
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