Biogenic silver nanoparticles synthesized from Piper longum fruit extract inhibit HIF-1α/VEGF mediated angiogenesis in prostate cancer cells

Abstract

In the present study, biogenic silver nanoparticles (PL-AgNPs) were synthesized by using Piper longum (PL) dried fruit extract and investigated the effect of PL-AgNPs on angiogenesis and signal transduction pathway of hypoxia-inducible factor alpha (HIF-1α)/vascular endothelial growth factor (VEGF) on human prostate cancer cells. The prepared PL-AgNPs were characterized by ultraviolet-visible (UV-vis) spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX) and dynamic light scattering (DLS) analysis. Potential cytotoxic and anti-angiogenic effects of PL-AgNPs were evaluated on PC-3 and DU-145 prostate cancer cells. Cytotoxicity was evaluated by MTT assay. The anti-angiogenic effect was investigated via a cell migration assay. Protein and mRNA levels of key angiogenesis related molecules such as VEGF and HIF-1α were evaluated via ELISA and qRT-PCR assays. UV-vis spectroscopy showed an absorbance peak at 450 nm confirming the PL-AgNPs synthesis. Various characterization techniques revealed that the average size of synthesized PL-AgNPs was below 100 nm. The cytotoxic effect was elevated in a concentration-dependent manner (p˂0.05). The biosynthesized PL-AgNPs inhibited cell migration and reduced the levels of both protein and mRNA levels of VEGF and HIF-1α in prostate cancer cells (p˂0.05). Results revealed that the PL extract with AgNO3 nanoparticles may be a potential candidate for developing novel anticancer and antiangiogenic compounds for prostate cancer.