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<p>Breast cancer and liver cancer are among the top cancer-related causes of death worldwide, and both have complex molecular heterogeneity and dysregulated oncogenic signaling pathways. Natural products from under-exploited biological sources could be potential candidates for the discovery of multi-targeted anticancer drugs. The therapeutic effect of bioactive compounds present in <i>Harpaphe haydeniana</i> was explored with the help of integrated computational tools such as GC–MS profiling, ADMET screening, network pharmacology, molecular docking and molecular dynamics simulation. Among the bioactive compounds identified through GC–MS analysis, 1-tetradecanol was prioritized for detailed investigation owing to its relatively high abundance, favorable pharmacokinetic and toxicity profile predicted through ADMET analysis, compliance with established drug-likeness criteria, and its ability to interact with multiple cancer-associated targets identified through network pharmacology screening. These characteristics suggested that 1-tetradecanol represented a biologically relevant candidate for subsequent molecular docking and molecular dynamics simulations aimed at evaluating its potential multi-target anticancer activity. To identify the critical cancer-associated molecular targets and pathways, target prediction, protein–protein interaction (PPI) network construction, hub gene analysis and KEGG pathway enrichment were carried out. Based on a network pharmacology approach, certain overlapping hub genes were determined for liver and breast cancer progression, such as <i>TP53</i>,<i> MYC</i>,<i> CTNNB1</i>,<i> PTEN</i>,<i> KRAS</i>,<i> SRC</i>,<i> STAT3</i>, and <i>ESR1</i>. These targets were shown to be strongly enriched in pathways linked to cell proliferation, regulation of apoptosis, hormone signaling, and oncogenic signaling pathways, by functional enrichment analysis. The molecular docking analysis revealed that the 1-tetradecanol had favorable binding interactions with major oncogenic proteins such as <i>ESR1</i> with a binding score of − 5.6&#xa0;kcal/mol, <i>SRC</i> with a binding score of − 5.1&#xa0;kcal/mol, and <i>KRAS</i> with a binding score of − 4.9&#xa0;kcal/mol, which was supported by stable hydrogen bond and hydrophobic interactions. The results showed that under physiological conditions, the protein–ligand complexes remained structurally stable and intact, as suggested by the molecular dynamics simulations, which exhibited stable RMSD, radius of gyration and binding free energies profiles. The study provides the computational insights into potential molecular mechanisms supporting the potential relevance of <i>H. haydeniana</i>-derived metabolites for future anticancer investigation. The bioactive molecules and hub targets identified here provide a scientific basis for future experiments and new therapeutic approaches for liver and breast cancer.</p>

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Network pharmacology and molecular dynamics analysis of harpaphe haydeniana-derived bioactive compounds against breast and liver cancer

  • 期刊论文

  • 发表日期：

    2026年6月30日

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  • Vijaydharssani Krishnaraj,
  • Horne Iona Averal,
  • Elavarasi Siddhaiyan

摘要

Breast cancer and liver cancer are among the top cancer-related causes of death worldwide, and both have complex molecular heterogeneity and dysregulated oncogenic signaling pathways. Natural products from under-exploited biological sources could be potential candidates for the discovery of multi-targeted anticancer drugs. The therapeutic effect of bioactive compounds present in Harpaphe haydeniana was explored with the help of integrated computational tools such as GC–MS profiling, ADMET screening, network pharmacology, molecular docking and molecular dynamics simulation. Among the bioactive compounds identified through GC–MS analysis, 1-tetradecanol was prioritized for detailed investigation owing to its relatively high abundance, favorable pharmacokinetic and toxicity profile predicted through ADMET analysis, compliance with established drug-likeness criteria, and its ability to interact with multiple cancer-associated targets identified through network pharmacology screening. These characteristics suggested that 1-tetradecanol represented a biologically relevant candidate for subsequent molecular docking and molecular dynamics simulations aimed at evaluating its potential multi-target anticancer activity. To identify the critical cancer-associated molecular targets and pathways, target prediction, protein–protein interaction (PPI) network construction, hub gene analysis and KEGG pathway enrichment were carried out. Based on a network pharmacology approach, certain overlapping hub genes were determined for liver and breast cancer progression, such as TP53, MYC, CTNNB1, PTEN, KRAS, SRC, STAT3, and ESR1. These targets were shown to be strongly enriched in pathways linked to cell proliferation, regulation of apoptosis, hormone signaling, and oncogenic signaling pathways, by functional enrichment analysis. The molecular docking analysis revealed that the 1-tetradecanol had favorable binding interactions with major oncogenic proteins such as ESR1 with a binding score of − 5.6 kcal/mol, SRC with a binding score of − 5.1 kcal/mol, and KRAS with a binding score of − 4.9 kcal/mol, which was supported by stable hydrogen bond and hydrophobic interactions. The results showed that under physiological conditions, the protein–ligand complexes remained structurally stable and intact, as suggested by the molecular dynamics simulations, which exhibited stable RMSD, radius of gyration and binding free energies profiles. The study provides the computational insights into potential molecular mechanisms supporting the potential relevance of H. haydeniana-derived metabolites for future anticancer investigation. The bioactive molecules and hub targets identified here provide a scientific basis for future experiments and new therapeutic approaches for liver and breast cancer.