Enhanced pro-apoptotic and pro-oxidative effects of hesperidin on LNCaP prostate cancer cell line through nano-emulsification.

Using natural substances as adjuvant cancer therapy can help improve the condition of patients undergoing cancer treatment. Despite the fewer side effects of bioactive molecules, these substances still face many challenges. Nanotechnology can partially overcome these obstacles and increase the effectiveness of natural compounds many times over. Therefore, this research examined and contrasted the impact of hesperidin nanoemulsions (HES-NE) and free hesperidin (HES), with a significant focus on cell death pathways in (PCa) cells. qRT-PCR analysis revealed increased expression of the apoptotic genes P53 and Bax, and reduced expression of the anti-apoptotic gene Bcl-2, in cells treated with HES-NE. Caspase-3 enzyme activity assay indicated increased apoptosis in LNCaP cells treated with HES-NE. Furthermore, assessment of oxidative stress biomarkers revealed a dose-dependent increase in ROS and malondialdehyde (MDA) generation, and a decrease in superoxide dismutase (SOD) and glutathione peroxidase (GHS-Px) levels upon treatment with HES-NE. Our findings revealed that nanoformulated HES significantly enhanced its ability to induce apoptosis in PCa cells through P53/Bax/Bcl-2-mediated signaling pathways, compared to its free form.