2. Academic Validation
  3. Drug screening reveals the mechanism of toyocamycin-induced apoptosis in triple-negative breast cancer organoids

Drug screening reveals the mechanism of toyocamycin-induced apoptosis in triple-negative breast cancer organoids

  • Toxicol Appl Pharmacol. 2026 Jan:506:117659. doi: 10.1016/j.taap.2025.117659.
Houshi Ma 1,  Linlin Lu 2,  Yuqing Tu 2,  Xiaoran Chang 1,  Huabin Jiang 3,  Tianhang Yang 4,  Shun Wang 1,  Jinxian Wang 5,  Jinbing Xue 1,  Yan Chen 6,  Gangyin Luo 7
Affiliations

Affiliations

  • 1 Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China.
  • 2 The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
  • 3 College of Life Sciences, Shandong Normal University, 250014 Jinan, China.
  • 4 Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China; Jinan Guoke Medical Technology Development Co., Ltd, 250013 Jinan, China.
  • 5 Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China; School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China. Electronic address: [email protected].
  • 6 The First Affiliated Hospital of Soochow University, Suzhou 215006, China. Electronic address: [email protected].
  • 7 Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China; School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China. Electronic address: [email protected].
PMID: 41314261 DOI: 10.1016/j.taap.2025.117659
Abstract

Triple-negative breast Cancer (TNBC) is characterized by high aggressiveness and molecular heterogeneity, limiting therapeutic efficacy and drug resistance, necessitating reliable preclinical models and novel therapeutic agents. This study utilized tumor tissues derived from breast Cancer patients of various molecular subtypes, with a particular focus on TNBC, to construct patient-derived Organoid models (PDOs). These models effectively recapitulate the in vivo characteristics of tumors and provide a cost-effective platform for high-throughput drug screening. The study employed a label-free in vitro drug screening system based on bright-field imaging, which continuously monitors changes in Organoid area and brightness to assess the drug responses of 505 compounds. This approach avoids the interference associated with traditional cell viability assay reagents. Screening of the natural compound library using this system revealed that Toyocamycin effectively inhibits the growth of two TNBC Organoid models, exhibiting significant dose-dependency. Further mechanistic studies demonstrated that Toyocamycin induces Apoptosis in TNBC organoids by activating the p38 MAPK signaling pathway, specifically manifested by the upregulation of key genes such as TNFR, MAP3K7, MAP2K3, and DDIT3. It initially triggers cytotoxicity to suppress proliferation and subsequently induces sustained Apoptosis. This process can be reversed by the p38 inhibitor Adezmapimod, further confirming that its apoptosis-inducing effect is dependent on the p38 MAPK pathway. This study not only validates the reliability of patient-derived organoids in personalized drug screening but also uncovers the potential therapeutic value of Toyocamycin for TNBC, providing a novel model and theoretical foundation for the precision treatment of TNBC.

Keywords

Drug screening; Organoid; Toyocamycin; Triple-negative breast cancer.

Figures
Products
Inhibitors & Agonists
Other Products