TY - JOUR
T1 - 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
AU - Yu, Hsin Hsien
AU - Wu, Luo Yun
AU - Hsu, Pei Ling
AU - Lee, Chu Wan
AU - Su, Bor Chyuan
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Epinecidin-1
KW - Lipoteichoic acid
KW - Marine antimicrobial peptide
KW - Non-small-cell lung cancer
KW - Proliferation
KW - Epinecidin-1
KW - Lipoteichoic acid
KW - Marine antimicrobial peptide
KW - Non-small-cell lung cancer
KW - Proliferation
UR - http://www.scopus.com/inward/record.url?scp=85166301600&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85166301600&partnerID=8YFLogxK
U2 - 10.1007/s12602-023-10130-1
DO - 10.1007/s12602-023-10130-1
M3 - Article
C2 - 37523113
AN - SCOPUS:85166301600
SN - 1867-1306
VL - 16
SP - 1724
EP - 1733
JO - Probiotics and Antimicrobial Proteins
JF - Probiotics and Antimicrobial Proteins
IS - 5
ER -