Nile Tilapia Derived TP4 Shows Broad Cytotoxicity Toward to Non-Small-Cell Lung Cancer Cells

Area of Science:

• Biochemistry
• Oncology
• Pharmacology

Background:

• Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality globally.
• Current treatments like chemotherapy and targeted therapies face challenges including toxicity and drug resistance.
• There is an urgent need for novel therapeutic strategies for NSCLC.

Purpose of the Study:

• To investigate the cytotoxic effects of Tilapia piscidin (TP) 4, an antimicrobial peptide derived from Nile tilapia, on NSCLC cells.
• To evaluate the potential of TP4 as a monotherapy or in combination with Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for NSCLC treatment.

Main Methods:

• TP4 was tested for cytotoxicity against a panel of NSCLC cell lines with diverse genetic backgrounds.
• The mechanism of TP4-induced cell death was explored, focusing on necrosis.
• The efficacy of combining TP4 with EGFR-TKIs (Erlotinib, Gefitinib) was assessed in both EGFR-mutated and EGFR-wild-type NSCLC cells.

Main Results:

• TP4 demonstrated cytotoxicity against various NSCLC cell lines.
• TP4 was found to induce cell death via necrosis.
• Combination therapy of TP4 with Erlotinib or Gefitinib enhanced drug responses in EGFR-mutated NSCLC cells, but not in EGFR-wild-type cells.

Conclusions:

• TP4 is a potential therapeutic agent for NSCLC, exhibiting cytotoxic effects and inducing necrosis.
• Combining TP4 with EGFR-TKIs may offer a synergistic effect for treating EGFR-mutated NSCLC.
• This study highlights TP4 as a promising candidate for novel NSCLC treatment strategies, either alone or in combination therapies.