Antiproliferative and apoptotic effects of Pervari honey on SH-SY5Y neuroblastoma cells

Neuroblastoma is a complex and heterogeneous pediatric malignancy. Treatment options for neuroblastoma include surgery, chemotherapy, radiotherapy, autologous stem cell transplantation, and emerging immunotherapies. However, these approaches often coincide with oxidative stress, highlighting the potential role of natural antioxidants in chemoprevention and chemotherapy. Honey has long been recognized for its medicinal properties, including antimicrobial, anti-inflammatory, and antioxidant effects. Pervari honey (PH), produced by bees that forage on a diverse array of native flora, is a distinctive honey originating from southeastern Türkiye. This study evaluated the antiproliferative, anti-tumor, apoptotic, and inflammatory effects of PH on SH-SY5Y human neuroblastoma cells. Cell viability was measured using an MTT assay, while apoptosis was evaluated using an Annexin V-FITC/7-AAD staining test. The RT-qPCR method was used to quantify the expression of IL-1β, IL-6, TNF-α, NF-κB, Caspase-3, MMP-2, MMP-9, BAX, and BCL-2 genes. PH significantly reduced SH-SY5Y cell viability in a dose- and time-dependent manner (p < 0.05-p < 0.01). It induced apoptosis by upregulating BAX and Caspase-3 while downregulating BCL-2 (p < 0.05-p < 0.001). Additionally, it increased NF-κB expression (p < 0.05-p < 0.001) and modulated inflammatory (IL-1β, IL-6, and TNF-α) cytokines (p < 0.05-p < 0.01). MMP-2 and MMP-9 levels were significantly elevated (p < 0.05-p < 0.001), suggesting enhanced extracellular matrix remodeling. These in vitro findings indicate that PH may exert anti-tumor potential and possess immunomodulatory properties. Furthermore, in vitro and in vivo studies are needed to explore its therapeutic applicability.