# Indian medicinal phytocompounds for targeting apoptosis and high-penetrance genes in triple-negative breast cancer: an in-silico exploration

## TL;DR

This study explores how natural plant compounds might target genes involved in aggressive breast cancer, offering a new treatment approach.

## Contribution

The study identifies promising phytochemicals that bind effectively to key cancer-related genes in triple-negative breast cancer.

## Key findings

- Bayogenin showed strong binding to BRCA2 and PALB2 genes, outperforming the drug Olaparib in docking studies.
- Molecular dynamics simulations confirmed the stability of phytochemical-protein complexes over 200 ns.
- Phytochemicals may offer advantages over existing treatments by targeting multiple genes involved in TNBC.

## Abstract

Triple-negative breast cancer (TNBC) presents a significant therapeutic challenge due to its aggressive nature, lack of hormone receptors, and limited targeted treatment options. The complexity of the disease is further compounded by mutations in high-penetrance genes such as BRCA1, BRCA2, and BAX, along with other apoptotic genes involved in tumorigenesis, apoptosis, and drug resistance. Targeting these genes through innovative therapeutic approaches is crucial for improving treatment outcomes. This in-silico study explores the potential of phytochemicals as natural, multi-targeted therapeutic agents against high-penetrance and apoptotic genes implicated in TNBC. Using the IMPPAT 2.0 database, 300 phytochemicals were systematically screened based on their pharmacokinetic properties and toxicity profiles to identify promising candidates. Among them, Bayogenin exhibited strong binding to BRCA2 (-9.3 kcal/mol) and PALB2 (-8.7 kcal/mol), surpassing the FDA-approved drug Olaparib in molecular docking studies. Molecular dynamics simulations over 200 ns further confirmed the stability of these phytochemical-protein complexes, showing consistent root mean square deviation, hydrogen bonding, and free energy profiles. These findings highlight the therapeutic potential of phytochemicals and their possible advantages over existing TNBC treatments. By targeting key molecular pathways, this study provides insights into the development of natural, multi-targeted therapeutic strategies, emphasizing their translational relevance for TNBC therapy.

The online version contains supplementary material available at 10.1186/s12860-025-00548-6.