Dihydromyricetin suppresses tumor growth via downregulation of the EGFR/Akt/survivin signaling pathway

J Biochem Mol Toxicol. 2023 Jun;37(6):e23328. doi: 10.1002/jbt.23328. Epub 2023 Feb 19.

Abstract

Deregulation of epidermal growth factor receptor (EGFR) signaling is frequently observed in non-small cell lung cancer (NSCLC). The present study aimed to determine the impact of dihydromyricetin (DHM) on NSCLC, a natural compound extracted from Ampelopsis grossedentata with various pharmacological activities. Results of the present study demonstrated that DHM may act as a promising antitumor agent for NSCLC therapy, inhibiting the growth of cancer cells in vitro and in vivo. Mechanistically, results of the present study demonstrated that exposure to DHM downregulated the activity of wild-type (WT) and mutant EGFRs (mutations, exon 19 deletion, and L858R/T790M mutation). Moreover, western blot analysis indicated that DHM induced cell apoptosis via suppression of the antiapoptotic protein, survivin. Results of the present study further demonstrated that depletion or activation of EGFR/Akt signaling may regulate survivin expression though modulating ubiquitination. Collectively, these results suggested that DHM may act as a potential EGFR inhibitor, and may provide a novel choice of treatment strategy for patients with NSCLC.

Keywords: dihydromyricetin; epidermal growth factor receptor; non-small-cell lung cancer; survivin.

MeSH terms

  • Apoptosis
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Line, Tumor
  • Down-Regulation
  • ErbB Receptors / metabolism
  • Humans
  • Lung Neoplasms* / pathology
  • Mutation
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Survivin / metabolism

Substances

  • Survivin
  • ErbB Receptors
  • Proto-Oncogene Proteins c-akt
  • dihydromyricetin
  • Protein Kinase Inhibitors
  • EGFR protein, human