Marine Antimicrobial Peptide Epinecidin-1 Inhibits Proliferation Induced by Lipoteichoic acid and Causes cell Death in non-small cell lung cancer Cells via Mitochondria Damage

Abstract

Non-small cell lung cancer (NSCLC) is among the deadliest cancers worldwide. Despite the recent introduction of several new therapeutic approaches for the disease, improvements in overall survival and progression-free survival have been minimal. Conventional treatments for NSCLC include surgery, chemotherapy and radiotherapy. Except for surgery, these treatments can impair a patient’s immune system, leaving them susceptible to bacterial infections. As such, Staphylococcus aureus infections are commonly seen in NSCLC patients receiving chemotherapy, and a major constituent of the S. aureus cell surface, lipoteichoic acid (LTA), is thought to stimulate NSCLC cancer cell proliferation. Thus, inhibition of LTA-mediated cell proliferation might be a useful strategy for treating NSCLC. Epinecidin-1 (EPI), a marine antimicrobial peptide, exhibits broad-spectrum antibacterial activity, and it also displays anti-cancer activity in glioblastoma and synovial sarcoma cells. Furthermore, EPI has been shown to inhibit LTA-induced inflammatory responses in murine macrophages. Nevertheless, the anti-cancer and anti-LTA activities of EPI and the underlying mechanisms of these effects have not been fully tested in the context of NSCLC. In the present study, we demonstrate that EPI suppresses LTA-enhanced proliferation of NSCLC cells by neutralizing LTA and blocking its effects on toll-like receptor 2 and interleukin-8. Moreover, we show that EPI induces necrotic cell death via mitochondrial damage, elevated reactive oxygen species levels, and disrupted redox balance. Collectively, our results reveal dual anti-cancer activities of EPI in NSCLC, as the peptide not only directly kills cancer cells but it also blocks LTA-mediated enhancement of cell proliferation.

Anticancer activities of natural antimicrobial peptides from animals

“…In this research, piscidin-4 caused NSCLC cell death through the necrotic pathway rather than the apoptotic pathway. Another common peptide was epinecidin-1, a naturally occurring peptide isolated from orange-spotted grouper ( Epinephelus coioides ), which exhibited inhibitory activity on human lung cancer and glioblastoma by regulating the process of cell apoptosis and necrosis ( Su et al, 2020 ; Yu et al, 2023 ).…”

Temporin-GHaK Exhibits Antineoplastic Activity against Human Lung Adenocarcinoma by Inhibiting the Wnt Signaling Pathway through miRNA-4516

“…However, multi-drug resistance abolishes their benefit; therefore, there is an emergent need for new medicines to improve NSCLC therapy [ 4 , 5 ]. Yu HH et al investigated the use of the marine antimicrobial peptide (AMP) epinecidin-1 as a potential treatment for NSCLC and demonstrated its effectiveness in inhibiting tumor cell growth [ 6 ].…”

“…Molecules 2024, 29, 2797 2 of 16 AMPs are naturally occurring small peptides with less than 50 amino acids, often found in bacteria, archaea, protists, fungi, plants, and animals. They can eradicate invading pathogens and therefore play a critical role in the innate immune system [6][7][8][9]. Many AMPs have demonstrated antineoplastic properties.…”