Piperine inhibits colorectal cancer migration and invasion by regulating STAT3/Snail-mediated epithelial-mesenchymal transition

Biotechnol Lett. 2020 Oct;42(10):2049-2058. doi: 10.1007/s10529-020-02923-z. Epub 2020 Jun 4.


Cancer metastasis is the primary cause of death in patients diagnosed with colorectal cancer. Piperine, an active nontoxic ingredient in pepper, has potent anti-inflammatory and anti-cancer properties. However, little is known about the anti-migratory and anti-invasive effects of piperine on colorectal cancer. We demonstrated piperine inhibited the migration and invasion of colorectal cancer cells. Then, we found piperine reversed the biomarker expression of epithelial-to-mesenchymal transition (EMT), and suppressed the EMT regulator Snail. Furthermore, signal transducers and activators of transcription 3 (STAT3) was downregulated by piperine. Finally, STAT3 inhibitors were applied to observe the role of STAT3 in colorectal cancer migration, invasion and EMT. Collectively, piperine inhibits colorectal cancer migratory and invasive capacities through STAT3/Snail mediated EMT. Therefore, piperine could be applied as a possible therapeutic regimen for the prevention of colorectal cancer metastasis.

Keywords: Colorectal cancer; Epithelial–mesenchymal transition; Metastasis; Piperine; STAT3.

MeSH terms

  • Alkaloids / pharmacology*
  • Benzodioxoles / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Colorectal Neoplasms / metabolism*
  • Epithelial-Mesenchymal Transition / drug effects*
  • Humans
  • Piperidines / pharmacology*
  • Polyunsaturated Alkamides / pharmacology*
  • STAT3 Transcription Factor / metabolism*
  • Snail Family Transcription Factors / metabolism*


  • Alkaloids
  • Benzodioxoles
  • Piperidines
  • Polyunsaturated Alkamides
  • SNAI1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Snail Family Transcription Factors
  • piperine