Zingerone Facilitates Apoptosis in Triple Negative Breast Cancer Cells by Inducing Autophagy

J Biochem Mol Toxicol. 2024 Dec;38(12):e70074. doi: 10.1002/jbt.70074.

Abstract

Triple negative breast cancer (TNBC) is characterized by high heterogenicity and aggressiveness and autophagy plays a complicated role in cancer development. Zingerone is reported to possess multiple pharmacological activities, including antitumors. This study explored the biological role and the relevant mechanisms of zingerone in TNBC. Following zingerone treatment, the viability of normal breast cancer cells MCF-10A and TNBC cells (MDA-MB-231 and MDA-MB-468) was detected with CCK-8 assay. The proliferation, migration and invasion of TNBC cells were detected with colony formation, wound healing, and transwell assays. Western blot was used to detect the expressions of migration-, apoptosis- and autophagy-related proteins. Flow cytometry was used to detect the cell apoptotic level and immunofluorescence assay measured the autophagy. The experimental data revealed that zingerone with varying concentrations suppressed cell viability, proliferation, migration and invasion while promoting the apoptosis in TNBC, which might be mediated by autophagy activation. Besides, zingerone decreased HDAC1 expression in TNBC cells and regulated autophagy via HDAC1. Collectively, zingerone impeded the malignant progression of TNBC via inducing HDAC1-mediated autophagy.

Keywords: HDAC1; apoptosis; autophagy; triple negative breast cancer; zingerone.

MeSH terms

  • Apoptosis* / drug effects
  • Autophagy* / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Female
  • Guaiacol* / analogs & derivatives
  • Guaiacol* / pharmacology
  • Histone Deacetylase 1 / metabolism
  • Humans
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / metabolism
  • Triple Negative Breast Neoplasms* / pathology

Substances

  • Guaiacol
  • zingerone
  • HDAC1 protein, human
  • Histone Deacetylase 1