Antimicrobial peptide moricin induces ROS mediated caspase-dependent apoptosis in human triple-negative breast cancer via suppression of notch pathway

Imran Ahmad; Saurabh Pal; Ranjana Singh; Khursheed Ahmad; Nilanjan Dey; Aditi Srivastava; Rumana Ahmad; Muath Suliman; Mohammad Y Alshahrani; Md Abul Barkat; Sahabjada Siddiqui

doi:10.1186/s12935-023-02958-y

Antimicrobial peptide moricin induces ROS mediated caspase-dependent apoptosis in human triple-negative breast cancer via suppression of notch pathway

Cancer Cell Int. 2023 Jun 21;23(1):121. doi: 10.1186/s12935-023-02958-y.

Authors

Affiliations

¹ Department of Biochemistry, King George's Medical University, Lucknow, 226003, India. imranahmadysbiochem@kgmcindia.edu.
² Department of Biotechnology, Era's Lucknow Medical College & Hospital, Era University, Lucknow, 226003, India.
³ Department of Biochemistry, King George's Medical University, Lucknow, 226003, India. ranjanasingh@kgmcindia.edu.
⁴ Department of Chemistry, BITS- Pilani Hyderabad Campus, Hyderabad, 500078, Telangana, India.
⁵ Department of Biochemistry, Era's Lucknow Medical College & Hospital, Era University, Lucknow, 226003, India.
⁶ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
⁷ Department of Pharmaceutics, College of Pharmacy, University of Hafr Al-Batin, Al Jamiah, Hafr Al Batin, 39524, Saudi Arabia.
⁸ Department of Biotechnology, Era's Lucknow Medical College & Hospital, Era University, Lucknow, 226003, India. sahabjadabiotech04@gmail.com.

^# Contributed equally.

Abstract

Background: Breast cancer is the world's most prevalent cancer among women. Microorganisms have been the richest source of antibiotics as well as anticancer drugs. Moricin peptides have shown antibacterial properties; however, the anticancer potential and mechanistic insights into moricin peptide-induced cancer cell death have not yet been explored.

Methods: An investigation through in silico analysis, analytical methods (Reverse Phase-High Performance Liquid Chromatography (RP-HPLC), mass spectroscopy (MS), circular dichroism (CD), and in vitro studies, has been carried out to delineate the mechanism(s) of moricin-induced cancer cell death. An in-silico analysis was performed to predict the anticancer potential of moricin in cancer cells using Anti CP and ACP servers based on a support vector machine (SVM). Molecular docking was performed to predict the binding interaction between moricin and peptide-related cancer signaling pathway(s) through the HawkDOCK web server. Further, in vitro anticancer activity of moricin was performed against MDA-MB-231 cells.

Results: In silico observation revealed that moricin is a potential anticancer peptide, and protein-protein docking showed a strong binding interaction between moricin and signaling proteins. CD showed a predominant helical structure of moricin, and the MS result determined the observed molecular weight of moricin is 4544 Da. An in vitro study showed that moricin exposure to MDA-MB-231 cells caused dose dependent inhibition of cell viability with a high generation of reactive oxygen species (ROS). Molecular study revealed that moricin exposure caused downregulation in the expression of Notch-1, NF-ƙB and Bcl2 proteins while upregulating p53, Bax, caspase 3, and caspase 9, which results in caspase-dependent cell death in MDA-MB-231 cells.

Conclusions: In conclusion, this study reveals the anticancer potential and underlying mechanism of moricin peptide-induced cell death in triple negative cancer cells, which could be used in the development of an anticancer drug.

Keywords: Anticancer peptide; Apoptosis; Moricin; Notch1; Triple negative breast cancer.