Objective: This study investigated the therapeutic potential of green-synthesized zinc oxide nanoparticles (ZnO NPs) derived from aqueous extract of Portulaca oleracea aerial parts as a novel, biocompatible agent against gastric cancer. Given the limitations of conventional treatments, including drug resistance and systemic toxicity, targeted anticancer strategies are urgently needed.
Materials and Methods: The synthesized ZnO NPs were characterized using TEM, FESEM, AFM, and XRD. Their cytotoxic effects were evaluated in AGS human gastric cancer cells and normal HEK-293 cells using the MTT assay. Apoptotic mechanisms were investigated by Annexin V-PI staining, DAPI staining, and gene expression analysis of Bax, P53, Caspase-3, Caspase-9, and Bcl-2. The anti-angiogenic activity of the NPs was assessed using the chorioallantoic membrane (CAM) assay.
Results: The ZnO NPs exhibited significant concentration- and time-dependent cytotoxicity against AGS cells, while causing minimal toxicity in HEK-293 cells. The antioxidant assay revealed significant concentration- and time-dependent antioxidant activity, with enhanced effects following prolonged exposure. Apoptosis was identified as the primary mechanism of cell death, as demonstrated by morphological alterations, increased apoptotic cell populations, and upregulation of pro-apoptotic genes, accompanied by downregulation of the anti-apoptotic Bcl-2 gene. In the CAM model, the NPs showed potent, dose-dependent anti-angiogenic activity by reducing vascular branching and vessel length and adversely affecting embryo development.
Conclusion: Green-synthesized P. oleracea-derived ZnO NPs exerted anticancer effects through the combined induction of apoptosis, inhibition of angiogenesis, and antioxidant activity. These findings support their potential as a promising complementary nanotherapeutic strategy for gastric cancer treatment.