期刊
BIOCHIMIE
卷 201, 期 -, 页码 7-17出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biochi.2022.06.011
关键词
Non-small cell lung cancer; Antimicrobial peptides; D-LAK; Mitochondria-mediateda poptosis; Cell-cycle arrest
资金
- College of Pharmacy and Health Sciences (CPHS), St. John's University
- Department of Pharmaceutical Sciences, CPHS, St. John's University
D-LAK, a cationic antimicrobial peptide, exhibits strong cytotoxicity against non-small cell lung cancer cell lines, inducing cell apoptosis and arresting the cell cycle, inhibiting cell proliferation and cancer cell migration, and leading to mitochondria-mediated apoptosis. It acts by disrupting the cell membrane.
Non-small cell lung cancer (NSCLC) is a major cause of global cancer mortalities and accounts for approximately 80-85% of reported lung cancer cases. Conventional chemotherapeutics show limited application because of poor tumor selectivity and acquired drug resistance. Antimicrobial peptides (AMPs) have gained much attention as potential anticancer therapeutics owing to their high potency and high target selectivity and specificity with limited scope for drug resistance. In this study, D-LAK (D-LAK -120A), a cationic AMP, was evaluated for its anticancer efficacy in various NSCLC cell lines. D-LAK peptide demonstrated enhanced cytotoxicity in A549, H358, H1975, and HCC827 cell lines with inhibitory con-centrations between 4.0 and 5.5 mM. An increase in the lactate dehydrogenase (LDH) levels and propi-dium iodide (PI) uptake across compromised membrane suggested membranolytic activity as an inhibition pathway. In addition, we found D-LAK induced lung cancer cell apoptosis and arrested cells in the S phase (DNA synthesis) of cell cycle. Moreover, a decreased mitochondrial membrane potential and elevated ROS levels were observed after D-LAK treatment, suggesting induction of mitochondria-mediated apoptosis. Additionally, D-LAK inhibited single cell proliferation and cancer cell migration in vitro. The tumor reduction observed in the 3D spheroid assay further suggests the potential use of D -LAK as an anticancer agent for NSCLC treatment. Our results postulate innovative insights on the anti-cancer mechanism of D-LAK, which may contribute to its further development into preclinical studies and a potential therapeutic.(c) 2022 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.
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