Anticancer activities of novel hyper-charged antimicrobial peptides

• Main Author: Yeo, Ivory Ching Yee
• Other Authors: Navin Verma
• Format: Final Year Project
• Language: English
• Published: 2018
• Subjects: DRNTU::Science::Biological sciences::Molecular biology
• Online Access: http://hdl.handle.net/10356/74169
• Institution: Nanyang Technological University

Background: Antimicrobial peptides (AMPs) have been shown to exhibit anticancer activity due to their unique properties. This study aims to screen a panel of hyper-charged (HC) AMPs with anti-proliferative activity and investigate the molecular mechanism in cutaneous T-cell lymphoma (CTCL), a non-Hodgkin lymphoma that is a leading cause of morbidity and mortality. Results: A panel of eight HC AMPs were screened using MTS assay against three CTCL cell lines (HuT78, MJ, HH), two DLBCL cell lines (Ly-4, Ly-18), human lung epithelial cell line A549, primary dermal fibroblasts and primary T-cells. HC-3 and HC-5 peptides showed significant anti-proliferative activity against hematolymphoid cells with IC50 ranging from 50 to 200 µg/ml. Both peptides were found to be non-toxic to human lung epithelial cells and dermal fibroblasts. Flow cytometry showed that HC-3 and HC-5 peptides induced apoptosis in hematolymphoid cells but not in primary healthy T-cells. Lastly, Western immunoblotting suggested that HC peptide-mediated cell death occured in a caspase- and PARP- dependent manner. Both peptides suppressed STAT3 phosphorylation in CTCL cells. Conclusion: This study identified HC-3 and HC-5 peptides as novel anticancer agents targeting hematolymphoid cells. Our findings thus have implications in the development of new generation therapeutics for cutaneous lymphomas.