In Vitro Effects of Papaverine on Cell Migration and Vascular Endothelial Growth Factor in Cancer Cell Lines

Int J Mol Sci. 2022 Apr 22;23(9):4654. doi: 10.3390/ijms23094654.

Abstract

Papaverine (PPV) is a benzylisoquinoline alkaloid isolated from Papaver somniferum that exerts antiproliferative activity. However, several questions remain regarding the biochemical pathways affected by PPV in tumourigenic cells. In this study, the influence of PPV on cell migration (light microscopy), expression of vascular endothelial growth factor (VEGF) B, VEGF R1, VEGF R2, and phosphorylated focal adhesion kinase (pFAK) were investigated using spectrophotometry in MDA-MB-231-, A549- and DU145 cell lines. The migration assay revealed that, after 48 h, PPV (100 µM) reduced cell migration to 81%, 91%, and 71% in MDA-MB-231-, A549-, and DU145 cells, respectively. VEGF B expression was reduced to 0.79-, 0.71-, and 0.73-fold after 48 h of exposure to PPV in MDA-MB-231-, A549- and DU145 cells, while PPV exposure of 48 h increased VEGF R1 expression in MDA-MB-231- and DU145 cells to 1.38 and 1.46. A fold decrease in VEGF R1 expression was observed in A549 cells to 0.90 after exposure to 150 µM. No statistically significant effects were observed on VEGF R2- and FAK expression after exposure to PPV. This study contributes to the understanding of the effects of a phytomedicinal alkaloid compound in cancer cells and may provide novel approaches to the application of non-addictive alkaloids.

Keywords: VEGF B; VEGF R1; VEGF R2; cancer; cell migration; pFAK; papaverine.

MeSH terms

  • Antineoplastic Agents
  • Cell Line
  • Cell Movement* / drug effects
  • Humans
  • Neoplasms*
  • Papaverine* / pharmacology
  • Vascular Endothelial Growth Factor A* / drug effects
  • Vascular Endothelial Growth Factor A* / metabolism
  • Vascular Endothelial Growth Factors

Substances

  • Antineoplastic Agents
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Papaverine