In silico identification and in vitro assessment of a potential anti-breast cancer activity of antimicrobial peptide retrieved from the ATMP1 Anabas testudineus fish peptide

PeerJ

article

Douglas Law¹  Ahmed Abdulkareem Najm²  Jia Xuan Chong¹  Joelene Zi Ying K’ng¹  Mas Amran¹  Huey Lih Ching¹  Rui Rui Wong¹  May Ho Leong¹  Ibrahim Mahmood Mahdi¹  Shazrul Fazry² 

[1]Faculty of Health and Life Sciences, INTI International University

[2]Department of Food Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia

[3]Molecular Diagnostic Department

关键词: Anabas testudineus;    Antimicrobial peptide;    Breast cancer;    Peptide drug;   

DOI  :  10.7717/peerj.15651

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

A previous study has shown that synthetic antimicrobial peptides (AMPs) derived from Anabas testudineus (ATMP1) could in-vitro inhibit the progression of breast cancer cell lines. In this study, we are interested in studying altered versions of previous synthetic AMPs to gain some insight into the peptides functions. The AMPs were altered and subjected to bioinformatics prediction using four databases (ADP3, CAMP-R3, AMPfun, and ANTICP) to select the highest anticancer activity. The bioinformatics in silico analysis led to the selection of two AMPs, which are ATMP5 (THPPTTTTTTTTTTTYTAAPATTT) and ATMP6 (THPPTTTTTTTTTTTTTAAPARTT). The in silico analysis predicted that ATMP5 and ATMP6 have anticancer activity and lead to cell death. The ATMP5 and ATMP6 were submitted to deep learning databases (ToxIBTL and ToxinPred2) to predict the toxicity of the peptides and to (AllerTOP & AllergenFP) check the allergenicity. The results of databases indicated that AMPs are non-toxic to normal human cells and allergic to human immunoglobulin. The bioinformatics findings led to select the highest active peptide ATMP5, which was synthesised and applied for in-vitro experiments using cytotoxicity assay MTT Assay, apoptosis detection using the Annexin V FTIC-A assay, and gene expression using Apoptosis PCR Array to evaluate the AMP’s anticancer activity. The antimicrobial activity is approved by the disc diffusion method. The in-vitro experiments analysis showed that ATMP5 had the activity to inhibit the growth of the breast cancer cell line (MDA-MB-231) after 48 h and managed to arrest the cell cycle of the MDA-MB-231, apoptosis induction, and overexpression of the p53 by interaction with the related apoptotic genes. This research opened up new opportunities for developing potential and selective anticancer agents relying on antimicrobial peptide properties.

【 授权许可】

CC BY