Naphthoquinone-derived ZSW-4B induces apoptosis in triple-negative breast cancer via AMPK signalling activation

Sci Rep. 2024 Nov 19;14(1):28559. doi: 10.1038/s41598-024-79592-9.

Abstract

Triple-negative breast cancer (TNBC) is the most malignant molecular subtype of breast cancer and is characterized by aggressiveness, high mortality, significant heterogeneity, and poor prognosis. AMPK plays a critical role in maintaining the cellular energy balance, and its inactivation is associated with malignant breast cancer. Here, we identified the pharmacological mechanism of the 1,4-naphthoquinone derivative ZSW-4B. MTT, colony formation, and nude mouse xenograft tumour models demonstrated that ZSW-4B selectively inhibits the proliferation of TNBC cells both in vitro and in vivo. Flow cytometry and Western blot analysis revealed that ZSW-4B induces apoptosis in TNBC cells. Phosphoproteomic analysis revealed activation of the AMPK signalling pathway by ZSW-4B. Additionally, the application of the CRISPR-Cas9 system to genetically knockout AMPK in TNBC cell lines was demonstrated to reverse the antitumour effects elicited by ZSW-4B both in vitro and in vivo. In summary, ZSW-4B inhibits TNBC by inducing cellular apoptosis through the activation of AMPK.

MeSH terms

  • AMP-Activated Protein Kinases* / metabolism
  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis* / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Naphthoquinones* / pharmacology
  • Signal Transduction* / drug effects
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / genetics
  • Triple Negative Breast Neoplasms* / metabolism
  • Triple Negative Breast Neoplasms* / pathology
  • Xenograft Model Antitumor Assays*

Substances

  • Naphthoquinones
  • AMP-Activated Protein Kinases
  • Antineoplastic Agents