Dictamnine inhibits pancreatic cancer cell growth and epithelial-mesenchymal transition by blocking the PI3K/AKT signaling pathway

Neoplasma. 2022 May;69(3):603-619. doi: 10.4149/neo_2022_211016N1474. Epub 2022 Mar 10.

Abstract

Many different treatments are available for pancreatic cancer (PC), including surgical resection, chemotherapy, radiotherapy, and immunotherapy, but these treatments are often ineffective at curing PC. Hence, identifying new and effective agents or strategies to improve therapeutic effects is critical. This study focused on the efficacy of dictamnine (DTM), a furan quinoline alkaloid extracted from Dictamnus dasycarpus Turcz., in treating PC. Our in vitro results showed that DTM can mitigate cell proliferation and induce cell cycle arrest and apoptosis in two different human PC cell lines. Moreover, epithelial-mesenchymal transition (EMT) was prevented during DTM treatment, reflected by reduced cell migration and invasion abilities. In vivo studies demonstrated that DTM treatment led to a remarkable inhibition of tumor growth in a xenograft nude mouse model. Mechanistic investigation showed that DTM might act by restraining constitutive and induced PI3K/AKT activity. In summary, our results demonstrated that DTM slows PC progression by inhibiting the activity of the PI3K/AKT signaling pathway and its downstream effectors and that DTM is effective as a pathway-specific cancer therapy. These findings could provide a greater understanding of the function of anticancer drugs and new options for PC treatment.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quinolines* / pharmacology
  • Signal Transduction

Substances

  • Quinolines
  • Proto-Oncogene Proteins c-akt
  • dictamnine