In vitro antiproliferative effects of green synthesized silver nanoparticles from Brassica carinata microgreens on DU-145 prostate cancer cells and In vivo safety assessment

Abstract

Background

Prostate cancer ranks among the most lethal malignancies affecting men globally. Conventional therapeutic approaches for this disease encounter limitations due to adverse side effects and the emergence of drug resistance, making its management challenging. Green-synthesized silver nanoparticles (AgNPs) have emerged as an attractive alternative to address the shortcomings of existing anticancer treatments.

Objective

This study was undertaken to evaluate the anticancer potential and safety profile of BCM-AgNPs, focusing on DU-145 inhibition and sub-acute toxicity in Wistar rats.

Methods

Previously synthesized Brassica carinata microgreen silver nanoparticles (BCM-AgNPs) alongside Brassica carinata microgreen crude extract (BCME) were used. The antiproliferative activity was investigated through the MTT assay on DU-145 prostate cancer cells and normal Vero E6 cells to determine the IC₅₀ and CC₅₀. Subsequently, a series of bioassays, including cell migration assays, clonogenic assays, cell cycle assays, and DNA fragmentation assays, were conducted. Furthermore, RT-qPCR was performed to delineate the molecular mechanism of BCM-AgNPs on DU-145 cells. Finally, a subacute toxicity study was carried out to assess the safety of BCM-AgNPs.

Results

Both BCM-AgNPs and BCME exhibited potent antiproliferative activity against DU-145 cells with an IC₅₀ of 33.47 μg/mL and 46.25 μg/mL, respectively, while sparing normal Vero E6 cells with selectivity indices of 3.50 for BCM-AgNPs and 4.62 for BCME. BCM-AgNPs demonstrated anti-migratory effects and hindered colony formation in DU-145 cells. They further induced S-phase cell cycle arrest through DNA fragmentation. RT-qPCR analysis revealed the upregulation of pro-apoptotic genes and the downregulation of genes involved in cell survival and proliferation pathways. BCM-AgNPs showed no toxicity in Wistar rats during 28-day oral administration.

Conclusion

This study demonstrates for the first time the selective and prominent antiproliferative effects of BCM-AgNPs against DU-145, as well as their safety and biocompatibility, underscoring their potential as a promising candidate for anticancer therapy.