Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Exp Med. Dec 20, 2023; 13(5): 142-155
Published online Dec 20, 2023. doi: 10.5493/wjem.v13.i5.142
Exploring the mechanism of action bitter melon in the treatment of breast cancer by network pharmacology
Kavan Panchal, Bhavya Nihalani, Utsavi Oza, Aarti Panchal, Bhumi Shah
Kavan Panchal, Bhavya Nihalani, Utsavi Oza, Aarti Panchal, Bhumi Shah, Pharmaceutical Chemistry, L. J. Institute of Pharmacy, L J University, Gujarat, Ahmedabad 382210, India
Author contributions: Panchal K designed, performed and wrote the paper; Nihalani B designed, performed and wrote the paper; Oza U edited the paper; Panchal A edited the paper; Shah B designed, supervised and edited the paper.
Conflict-of-interest statement: The authors declare no conflicts of interest in this paper.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Bhumi Shah, PhD, Associate Professor, Pharmaceutical Chemistry, L. J. Institute of Pharmacy, L J University, Sanand Circle, Sarkhej-Gandhinagar Hwy, Sarkhej, Gujarat, Ahmedabad 382210, India. bhumi197@gmail.com
Received: September 22, 2023
Peer-review started: September 22, 2023
First decision: September 29, 2023
Revised: October 4, 2023
Accepted: October 30, 2023
Article in press: October 30, 2023
Published online: December 20, 2023
Processing time: 87 Days and 20.6 Hours
Abstract
BACKGROUND

Bitter melon has been used to stop the growth of breast cancer (BRCA) cells. However, the underlying mechanism is still unclear.

AIM

To predict the therapeutic effect of bitter melon against BRCA using network pharmacology and to explore the underlying pharmacological mechanisms.

METHODS

The active ingredients of bitter melon and the related protein targets were taken from the Indian Medicinal Plants, Phytochemistry and Therapeutics and SuperPred databases, respectively. The GeneCards database has been searched for BRCA-related targets. Through an intersection of the drug’s targets and the disease’s objectives, prospective bitter melon anti-BRCA targets were discovered. Gene ontology and kyoto encyclopedia of genes and genomes enrichment analyses were carried out to comprehend the biological roles of the target proteins. The binding relationship between bitter melon’s active ingredients and the suggested target proteins was verified using molecular docking techniques.

RESULTS

Three key substances, momordicoside K, kaempferol, and quercetin, were identified as being important in mediating the putative anti-BRCA effects of bitter melon through the active ingredient-anti-BRCA target network study. Heat shock protein 90 AA, proto-oncogene tyrosine-protein kinase, and signal transducer and activator of transcription 3 were found to be the top three proteins in the protein-protein interaction network study. The several pathways implicated in the anti-BRCA strategy for an active component include phosphatidylinositol 3-kinase/protein kinase B signaling, transcriptional dysregulation, axon guidance, calcium signaling, focal adhesion, janus kinase-signal transducer and activator of transcription signaling, cyclic adenosine monophosphate signaling, mammalian target of rapamycin signaling, and phospholipase D signaling.

CONCLUSION

Overall, the integration of network pharmacology, molecular docking, and functional enrichment analyses shed light on potential mechanisms underlying bitter melon’s ability to fight BRCA, implicating active ingredients and protein targets, as well as highlighting the major signaling pathways that may be altered by this natural product for therapeutic benefit.

Keywords: Bitter melon; Momordica charantia; Network pharmacology; Molecular docking; Breast cancer; Indian Medicinal Plants, Phytochemistry and Therapeutics

Core Tip: The phytochemicals and molecular processes in bitter melon that are thought to be involved in the therapy of breast cancer (BRCA) were investigated using network Pharmacology. Our research demonstrated that the anti-BRCA benefits of bitter melon are likely caused by negative regulation of transcription, cell differentiation, apoptosis, proteolysis, negative control of neuron apoptosis, and cell migration. Further discovered nine important pathways like phosphatidylinositol 3-kinase/protein kinase B signaling, transcriptional dysregulation, axon guidance, calcium signaling, focal adhesion, janus kinase-signal transducer and activator of transcription signaling, cyclic adenosine monophosphate signaling, mammalian target of rapamycin signaling, and phospholipase D signaling, are likely to be involved in the mechanism of action of bitter melon for the treatment of BRCA.