Berberine inhibits the malignant cell phenotype by inactivating PI3K/AKT/mTOR signaling in laryngeal squamous cell carcinoma

Histol Histopathol. 2024 Nov;39(11):1527-1536. doi: 10.14670/HH-18-753. Epub 2024 Apr 23.

Abstract

Background: Berberine is an active compound found in different herbs used in Chinese medicine and is well-known for its potential anticancer properties. The study aimed to figure out the role of berberine in regulating the malignant behavior of laryngeal squamous cell carcinoma (LSCC) cells.

Methods: LSCC cell lines (SNU-899 and AMC-HN-8) were treated with different concentrations of berberine (0-200 μM) to determine its cytotoxicity. The migration, invasion, and apoptosis of LSCC cells were measured by wound healing assays, Transwell assays, and flow cytometry. Western blot was performed for the quantification of proteins involved in PI3K/AKT/mTOR signaling.

Results: The viability of LSCC cells was dose-dependently reduced by berberine. Berberine dampened LSCC cell migration and invasion while augmenting cell apoptosis, as evidenced by a reduced wound closure rate, a decrease in invaded cell number, and a surge in cell apoptosis in the context of berberine stimulation. Importantly, the effects of berberine on the cancer cell process were enhanced by LY294002 (an inhibitor for PI3K) treatment. Moreover, the protein levels of phosphorylated PI3K, AKT, and mTOR were markedly reduced in response to berberine treatment.

Conclusion: Berberine inhibits cell viability, migration, and invasion but augments cell apoptosis by inactivating PI3K/AKT/mTOR signaling in LSCC.

MeSH terms

  • Apoptosis* / drug effects
  • Berberine* / pharmacology
  • Carcinoma, Squamous Cell* / drug therapy
  • Carcinoma, Squamous Cell* / metabolism
  • Carcinoma, Squamous Cell* / pathology
  • Cell Line, Tumor
  • Cell Movement* / drug effects
  • Cell Survival / drug effects
  • Humans
  • Laryngeal Neoplasms* / drug therapy
  • Laryngeal Neoplasms* / metabolism
  • Laryngeal Neoplasms* / pathology
  • Neoplasm Invasiveness
  • Phenotype
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction* / drug effects
  • Squamous Cell Carcinoma of Head and Neck / drug therapy
  • Squamous Cell Carcinoma of Head and Neck / metabolism
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • TOR Serine-Threonine Kinases* / metabolism

Substances

  • Berberine
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • MTOR protein, human
  • Phosphatidylinositol 3-Kinases