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<p>Breast cancer is the most common cancer among women. Currently, most treatments involve combinations of multiple therapies. However, existing drug therapies remain limited by side effects and drug resistance. (1E,4E)- 1,7-bis(4-hydroxyphenyl)hepta- 1,4-dien- 3-one (DHDK) is a safer, potential targeted drug with strong anti-cancer activity, derived from mistletoe. However, few studies have explored its related treatment mechanisms. This study combined network pharmacology, bioinformatics, molecular docking, and experimental verification to elucidate the mechanism of action of DHDK in treating breast cancer. The SwissTargetPrediction database, Therapeutic Target Databases, and Comparative Toxicogenomics Databases were used for drug target identification. The Gene Expression Omnibus (GEO) database was employed for differential gene screening. The GeneCards, Online Mendelian Inheritance in Man (OMIM) database, and Therapeutic Target Databases (TTD) were utilized to identify DHDK’s breast cancer treatment targets. Nexus genes were identified using Cytoscape software after protein–protein interaction (PPI) analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) Resource were conducted to investigateunderlying mechanisms. Target were identified through molecular docking, and the selected signaling pathway was validatedby qPCR. Comprehensive analysis yielded possible targets and mechanisms: DHDK binds to JAK1, inhibiting the phosphorylation of tyrosine residues in downstream target proteins, recruiting and phosphorylating the transcription factor STAT, downregulating STAT1, and further inhibiting the downstream effector BCL2, ultimately inhibits the anti-apoptotic effect of tumor cells. Therefore, DHDK is a highly promising targeted anti-cancer drug. Clinical trial number: not applicable.</p> Graphical abstract <p></p>

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Network pharmacology, bioinformatics analysis, and experimental validation to reveal the target and pharmacological mechanism of DHDK in treating breast cancer

  • 期刊论文

  • 发表日期：

    2025年4月14日

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  • Lin Meng,
  • Xinyue Wang,
  • Fangyu Zhang,
  • Meiyan Zhang,
  • Yuqing Wang,
  • Dingjia Guo,
  • Jing Hong,
  • Yunli Zhao

摘要

Breast cancer is the most common cancer among women. Currently, most treatments involve combinations of multiple therapies. However, existing drug therapies remain limited by side effects and drug resistance. (1E,4E)- 1,7-bis(4-hydroxyphenyl)hepta- 1,4-dien- 3-one (DHDK) is a safer, potential targeted drug with strong anti-cancer activity, derived from mistletoe. However, few studies have explored its related treatment mechanisms. This study combined network pharmacology, bioinformatics, molecular docking, and experimental verification to elucidate the mechanism of action of DHDK in treating breast cancer. The SwissTargetPrediction database, Therapeutic Target Databases, and Comparative Toxicogenomics Databases were used for drug target identification. The Gene Expression Omnibus (GEO) database was employed for differential gene screening. The GeneCards, Online Mendelian Inheritance in Man (OMIM) database, and Therapeutic Target Databases (TTD) were utilized to identify DHDK’s breast cancer treatment targets. Nexus genes were identified using Cytoscape software after protein–protein interaction (PPI) analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) Resource were conducted to investigateunderlying mechanisms. Target were identified through molecular docking, and the selected signaling pathway was validatedby qPCR. Comprehensive analysis yielded possible targets and mechanisms: DHDK binds to JAK1, inhibiting the phosphorylation of tyrosine residues in downstream target proteins, recruiting and phosphorylating the transcription factor STAT, downregulating STAT1, and further inhibiting the downstream effector BCL2, ultimately inhibits the anti-apoptotic effect of tumor cells. Therefore, DHDK is a highly promising targeted anti-cancer drug. Clinical trial number: not applicable.

Graphical abstract