The Effect of Quercetin in the Yishen Tongluo Jiedu Recipe on the Development of Prostate Cancer through the Akt1-related CXCL12/ CXCR4 Pathway

Comb Chem High Throughput Screen. 2024;27(6):863-876. doi: 10.2174/1386207326666230530095355.

Abstract

Background: It remains a challenge to effectively treat prostate cancer (PCa) that affects global men's health. It is essential to find a natural alternative drug and explore its antitumor mechanism due to the serious toxic side effects of chemotherapy.

Methods: The targets and signaling pathways were analyzed by network pharmacology and verified by molecular docking and LC-MS. The proliferation, apoptosis, invasion, and migration of DU145 cells were detected by the CCK-8 method, flow cytometry, and Transwell, respectively. The Bcl-2, caspase-3, CXCL12, and CXCR4 expressions and Akt1 phosphorylation were determined by Western blot. Akt1 overexpression was applied to identify the involvement of the Akt1- related CXCL12/CXCR4 pathway in regulating PCa. Nude mouse tumorigenesis was performed to analyze the effect of quercetin on PCa in vivo.

Results: Network pharmacology analysis displayed that quercetin was the main active component of the Yishen Tongluo Jiedu recipe and Akt1 was the therapy target of PCa. LC-MS analysis showed that quercetin existed in the Yishen Tongluo Jiedu recipe, and molecular docking proved that quercetin bound to Akt1. Quercetin inhibited the proliferation of DU145 cells by upregulating caspase-3 and downregulating Bcl-2 expression, promoting apoptosis and reducing invasion and migration abilities. In vivo, quercetin downregulated CXCL12 and CXCR4 expressions and inhibited PCa development by the Akt1-related CXCL12/CXCR4 pathway.

Conclusion: As the active component of the Yishen Tongluo Jiedu recipe, quercetin inhibited PCa development through the Akt1-related CXCL12/CXCR4 pathway. This study provided a new idea for PCa treatment and a theoretical basis for further research.

Keywords: Akt1; CXCL12/CXCR4 pathway; PCa; Yishen Tongluo Jiedu recipe; network pharmacology.; quercetin.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Chemokine CXCL12* / metabolism
  • Drugs, Chinese Herbal* / chemistry
  • Drugs, Chinese Herbal* / pharmacology
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Docking Simulation
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / metabolism
  • Prostatic Neoplasms* / pathology
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Quercetin* / chemistry
  • Quercetin* / pharmacology
  • Receptors, CXCR4* / antagonists & inhibitors
  • Receptors, CXCR4* / metabolism
  • Signal Transduction / drug effects

Substances

  • Receptors, CXCR4
  • Quercetin
  • Chemokine CXCL12
  • Proto-Oncogene Proteins c-akt
  • CXCR4 protein, human
  • CXCL12 protein, human
  • Drugs, Chinese Herbal
  • AKT1 protein, human