Puerarin Inhibits Proliferation, Migration and Invasion of Colon Cancer Cells and Induces Apoptosis via Suppression of the PI3K/AKT Signaling Pathway

  • Pharmaceuticals (Basel). 2025 Sep 16;18(9):1378. doi: 10.3390/ph18091378.
Lin Chen  1  2  3  4  5 ,  Xuhong Li  1  3  4  5 ,  Shijie Zhao  1  3  4  5 ,  Mengyu Hao  2 ,  Heng Wang  2 ,  Zhi Zhou  2 ,  Xinyu Xiong  2 ,  Die Yuan  2 ,  Piao Luo  2 ,  Luwen Wang  1  3  4  5 ,  Di Pan  1  3  4  5 ,  Xiangchun Shen  1  3  4  5 ,  Yue Zhang  1  3  4  5 ,  Yan Chen  1  3  4  5
Affiliations
  • 1. State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, School of Pharmaceutical Sciences, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, China.
  • 2. Key Laboratory of Natural Product Composition and Efficacy of Qiannan Prefecture, Qiannan Medical College for Nationalities, Duyun 558000, China.
  • 3. The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province, School of Pharmaceutical Sciences, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, China.
  • 4. The Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, China.
  • 5. Key Laboratory of Novel Anti-Cancer Drug Targets Discovery and Application, School of Pharmaceutical Sciences, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang 561113, China.
PMID: 41011246 DOI: 10.3390/ph18091378
Abstract

Background: Colon Cancer is one of the most prevalent gastrointestinal malignancies worldwide, with high mortality and limited therapeutic options. Puerarin, a flavonoid compound derived from Pueraria lobata, has shown Anticancer potential, but its molecular mechanisms against colon Cancer remain unclear. Methods and Results: In this study, human colon Cancer Caco-2 cells were treated with various concentrations of puerarin. Cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and Apoptosis were evaluated using CCK-8, wound healing, Transwell, immunofluorescence, flow cytometry, and Western blot assays. Puerarin significantly inhibited Caco-2 cell proliferation in a dose- and time-dependent manner. It suppressed migration and invasion by increasing E-cadherin and reducing Vimentin expression. Apoptosis was induced via upregulation of Bax and downregulation of Bcl-2. Network pharmacology and KEGG analysis suggested PI3K/Akt signaling as a core regulatory pathway. Western blotting confirmed that puerarin reduced phosphorylation of PI3K and Akt. PI3K Activator 740 Y-P promoted EMT and inhibited Apoptosis, whereas puerarin and the PI3K Inhibitor LY294002 reversed these effects. Conclusions: Puerarin exerts significant antitumor effects on Caco-2 colon Cancer cells by inhibiting proliferation, migration, and EMT, while promoting Apoptosis. These effects are mediated primarily through suppression of the PI3K/Akt signaling pathway. This study provides a theoretical basis for the use of puerarin as a natural therapeutic agent in colon Cancer treatment.

Keywords
PI3K/AKT; apoptosis; colon cancer; epithelial–mesenchymal transition; puerarin.
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