Tachyplesin induces apoptosis in non-small cell lung cancer cells and enhances the chemosensitivity of A549/DDP cells to cisplatin by activating Fas and necroptosis pathway

Chem Biol Drug Des. 2021 Apr;97(4):809-820. doi: 10.1111/cbdd.13810. Epub 2020 Dec 5.

Abstract

Cisplatin has strong broad-spectrum anticancer activity and is one of the most effective anticancer drugs currently used. The clinical application of cisplatin has led to the resistance of cancer cells to cisplatin. Tachyplesin is an active, natural marine peptide with antitumour activity. In the present study, we investigated whether tachyplesin can be used in non-small cell lung cancer (NSCLC) A549 and H460 cells as well as the cisplatin-resistant human A549/DDP NSCLC cell line. The results revealed that tachyplesin treatment significantly inhibited proliferation and induced apoptosis in A549 and H460 cells and the combination of tachyplesin and cisplatin significantly suppressed migration and improved sensitivity to cisplatin in A549/DDP cells. Further mechanistic examination revealed that tachyplesin induced apoptosis in A549/DDP cells by increasing Fas, FasL and p-RIPK1 levels. These results indicated that tachyplesin induces lung cancer death by activating the Fas, mitochondrial and necroptosis pathways. Tachyplesin could be developed as a candidate drug for cisplatin-resistant NSCLC.

Keywords: cisplatin resistance; migration; necroptosis; non-small cell lung cancer; tachyplesin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimicrobial Cationic Peptides / pharmacology*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cisplatin / pharmacology
  • DNA-Binding Proteins / pharmacology*
  • Drug Resistance, Neoplasm / drug effects*
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Membrane Potential, Mitochondrial / drug effects
  • Necroptosis / drug effects
  • Peptides, Cyclic / pharmacology*
  • Up-Regulation / drug effects
  • fas Receptor / metabolism

Substances

  • Antimicrobial Cationic Peptides
  • Antineoplastic Agents
  • DNA-Binding Proteins
  • FAS protein, human
  • Peptides, Cyclic
  • fas Receptor
  • tachyplesin peptide, Tachypleus tridentatus
  • Cisplatin