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January 23, 2020International Journal of Molecular SciencesOpen Access

Low Dose of Penfluridol Inhibits VEGF-Induced Angiogenesis

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Authors

SSSuyash SrivastavaNational Institute of Technology HamirpurFZFatema Tuz ZahraAmerican International University-BangladeshNGNehal GuptaBirla Institute of Technology and Science, Pilani

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Implication

Preclinical study demonstrates that low-dose penfluridol inhibits VEGF-induced angiogenesis and cell migration in endothelial and cancer models, suggesting potential for repurposing in cancer therapy.

Key Points

  • To determine the effects of low, clinically relevant concentrations of penfluridol on the tumor microenvironment, specifically angiogenesis, compared to its direct effects on cancer cells.
  • Assessed in vitro endothelial cell cytotoxicity, cell migration, and capillary-like tube formation in primary endothelial cells stimulated with VEGF.
  • Evaluated in vivo vessel formation using VEGF- and FGF-stimulated matrigel plug assays.
  • Analyzed intracellular signaling cascades (VEGFR2, p38, ERK, Src, and Akt) alongside cancer cell motility and wound healing capacity.
  • Low-dose penfluridol demonstrated no cytotoxicity in endothelial cells while significantly blocking VEGF-induced endothelial migration and tube formation in vitro.
  • In vivo matrigel plug assays confirmed that penfluridol blocked VEGF- and FGF-driven neovascularization.
  • Penfluridol selectively abrogated VEGF-induced Src and Akt activation in endothelial cells without altering VEGFR2, p38, or ERK pathways, and mildly reduced basal Src activation and migration in cancer cells.

Cite This Study

Srivastava et al. (2020) studied this question.

synapsesocial.com/papers/6a7dab0133dcb27c99cb5313https://doi.org/10.3390/ijms21030755
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