Analysing potent biomarkers along phytochemicals for breast cancer therapy: an in silico approach

Abstract

Purpose: This research focused on the identification of herbal compounds as potential anti-cancer drugs, especially for breast cancer, that involved the recognition of Notch downstream targets NOTCH proteins (1-4) specifically expressed in breast tumours as biomarkers for prognosis, along with P53 tumour antigens, that were used as comparisons to check the sensitivity of the herbal bio-compounds.

Methods: After investigating phytochemical candidates, we employed an approach for computer-aided drug design and analysis to find strong breast cancer inhibitors. The present study utilized in silico analyses and protein docking techniques to characterize and rank selected bio-compounds for their efficiency in oncogenic inhibition for use in precise carcinomic cell growth control.

Results: Several of the identified phytocompounds found in herbs followed Lipinski's Rule of Five and could be further investigated as potential medicinal molecules. Based on the Vina score obtained after the docking process, the active compound Epigallocatechin gallate in green tea with NOTCH (1-4) and P53 proteins showed promising results for future drug repurposing. The stiffness and binding stability of green tea pharmacological complexes were further elucidated by the molecular dynamic simulations carried out for the highest scoring phytochemical ligand complex.

Conclusion: The target-ligand complex of green tea active compound Epigallocatechin gallate with NOTCH (1-4) had the potential to become potent anti-breast cancer therapeutic candidates following further research involving wet-lab experiments.

Keywords: Cancer cells; Docking; Herbal compounds; In silico analysis; Phytochemicals.

Fig. 1

Graphical representation of the methods employed in this study

Fig. 2

Types of proteins involved in Target retrieval. Source: Alpha fold Protein structural database

Fig. 3

Types of herbs and their active bio-compounds 3D conformers retrieved from PubChem database. Source: PubChem database

Fig. 4

A Binding site residue of P53 protein with phytochemicals, B NOTCH1 Protein, C NOTCH2 protein, and D NOTCH4 protein

Fig. 5

Docked poses of Green tea ligand Epigallocatechin gallate with P53 and NOTCH 1–4 proteins. Yellow-dotted lines represent Ionic/electrostatic interactions, teal-dotted lines represent strong hydrogen bonds, whilst hydrophobic interactions are represented by grey-dotted lines

Fig. 6

a Green tea active bio-compound Epigallocatechin gallate during MDS study. b RMSD plot filters based on time frame. c Root mean square deviation (RMSD) plot for ligand structure after three steps (Minimization, equilibration, production)

Fig. 7

a NOTCH3 protein-Green tea active bio-compound Epigallocatechin gallate before MDS study, b Target-ligand complex during minimization process, c Root mean square deviation (RMSD) plot for target-ligand complex after four steps (Minimization, equilibration, production)