Nile Tilapia Derived Antimicrobial Peptide TP4 Exerts Antineoplastic Activity Through Microtubule Disruption

Chen-Hung Ting1, Yi-Chung Liu2, Ping-Chiang Lyu3

  • 1Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, Ilan 262, Taiwan. koichiting@gmail.com.

Marine Drugs
|November 25, 2018
PubMed

Insights

Tilapia piscidin 4 (TP4), an antimicrobial peptide, kills lung cancer cells by disrupting their internal microtubule network. This disruption is crucial for TP4

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Antimicrobial peptides (AMPs) show potential anti-cancer effects through membrane lysis or intracellular actions.
  • Mechanisms of AMP-induced cancer cell death via intracellular effects are not fully understood.

Purpose of the Study:

  • To investigate the intracellular mechanisms of toxicity of a tilapia-derived antimicrobial peptide, Tilapia piscidin (TP) 4, in lung carcinoma cells.
  • To determine if TP4 targets the microtubule network and if this interaction contributes to its anti-cancer activity.

Main Methods:

  • Pull-down assays to identify TP4 interaction partners.
  • Molecular docking to analyze the binding interface between TP4 and its target.
  • Treatment of A549 lung carcinoma cells with TP4 and its mutants.
  • Microscopy to assess microtubule network integrity.
  • In vitro microtubule depolymerization assays.

Main Results:

  • TP4 was found to penetrate A549 cells and interact with α-Tubulin.
  • Specific residues (Phe1, Ile16, Arg23) on TP4 are critical for α-Tubulin binding.
  • TP4 treatment disrupted the microtubule network in A549 cells.
  • Mutations in these key residues abolished microtubule depolymerization and reduced TP4's cytotoxicity.

Conclusions:

  • TP4 targets and disrupts the microtubule network in lung carcinoma cells.
  • Microtubule disruption is a key mechanism underlying TP4-induced cancer cell death.
  • TP4 represents a potential therapeutic agent for lung cancer, with its anti-cancer activity linked to microtubule targeting.

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