Inhibitory effects of Bombyx mori antimicrobial peptide cecropins on esophageal cancer cells

Eur J Pharmacol. 2020 Nov 15:887:173434. doi: 10.1016/j.ejphar.2020.173434. Epub 2020 Aug 4.

Abstract

Bombyx mori antimicrobial peptides (BmAMPs) are important effectors in silkworm immune system. They can inhibit and kill a variety of bacteria and fungi. Recent studies have shown that some kinds of BmAMPs exert strong inhibitory effects on a variety of tumor cells. In the present study, the antitumor activity of BmAMP Cecropin A (BmCecA) and BmAMP Cecropin D (BmCecD) was investigated against human esophageal cancer cells and their antitumor mechanism preliminary explored. Cell Counting Kit-8 and colony formation assays indicated that BmCecA and BmCecD suppressed cell proliferation and reduced colony formation of both Eca109 and TE13 cells in a dose-dependent manner, but exhibited no inhibitory effect on normal human embryonic kidney 293T cells. Wound healing and invasion experiments indicated that both BmCecA and BmCecD inhibited migration and invasion of Eca109 and TE13 cells in vitro. Annexin V/propidium iodide staining and flow cytometry detection suggested that BmCecA induced the apoptosis of Eca109 cells in a dose-dependent manner. RT-qPCR and western blot analysis showed that BmCecA induced apoptosis of Eca109 cells through the activation of a mitochondria-mediated caspase pathway, the upregulation of B-cell lymphoma 2 (Bcl-2)-associated X protein and the downregulation of Bcl-2. In addition, BmCecA significantly inhibited the growth of xenograft tumors in Eca109-bearing mice. These results suggested that BmCecA and BmCecD might serve as potential therapeutic agents for the treatment of cancer in the future.

Keywords: Antimicrobial peptides; Antitumor; Apoptosis; Bombyx mori; Esophageal cancer.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Bombyx*
  • Cecropins / isolation & purification
  • Cecropins / pharmacology
  • Cecropins / therapeutic use*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / prevention & control*
  • Female
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Pore Forming Cytotoxic Proteins / isolation & purification
  • Pore Forming Cytotoxic Proteins / pharmacology
  • Pore Forming Cytotoxic Proteins / therapeutic use*

Substances

  • Cecropins
  • Pore Forming Cytotoxic Proteins