Effects of Pelargonium Sidoides Extract on Apoptosis and Oxidative Stress in Human Neuroblastoma Cells

<i>Background and Objectives:</i> Neuroblastoma is the most common extracranial solid tumor in children, often presenting challenges in treatment due to its clinical and genetic heterogeneity. This study investigated the anticancer potential of <i>Pelargonium sidoides</i> root extract on the human neuroblastoma cell line (SH-SY5Y). Using XTT assays, ELISA-based oxidative stress markers, and RT-PCR analysis of apoptotic genes, the study explored the extract's effects on cell proliferation, oxidative stress, and apoptosis. <i>Materials and Methods:</i> For the cell culture, SH-SY5Y human neuroblastoma cells were thawed, cultured, and maintained under appropriate conditions for experiments. The dose- and time-dependent activity of Pelorgonium sidoides extract on SH-SY5Y neuroblastoma cells was investigated by XTT assay. The change in the oxidative stress marker 8-Hydroxy-2'-deoxyguanosine (8-OhDG) level was determined by ELISA for the doses applied to the control group root extract at a concentration of 25 μg/mL. Total antioxidant status (TAS) and total oxidant status (TOS) were measured from the cells in the study group with the help of a commercial kit. The oxidative stress index (OSI) was calculated by dividing the TAS by the TOS and multiplying by 100. In order to evaluate the expression levels of apoptosis-related Bax, Bcl-2, Caspase-3, Caspase-8, and Caspase-9 genes at the mRNA level in control and dose group cells, RNA isolation was performed from the SH-SY5Y control and dose group cells (IC50 value). <i>Results:</i> It is observed that the <i>P. sidoides</i> substance inhibits proliferation in cells at 24 h (<i>p</i> < 0.05). As the dose increases, cell proliferation decreases (<i>p</i> < 0.05). The IC50 value was calculated to be 113.83 μg/mL at 24 h. The concentration of 8-OhDG increased in neuroblastoma cells as a result of <i>P. sidoides</i> extract treatment (<i>p</i> < 0.05). TOS levels increased in neuroblastoma cells treated with <i>P. sidoides</i> extract (<i>p</i> < 0.01). OSI levels increased in cells treated with <i>P. sidoides</i> extract (<i>p</i> < 0.001). BAX and Caspase-8 expression increased are statistically significant in the <i>P. sidoides</i> dose group (<i>p</i> < 0.05). <i>Conclusions: P. sidoides</i> extract induces apoptosis in neuroblastoma cells through oxidative stress and mitochondrial- and death receptor-mediated pathways. This study highlights the potential of <i>P. sidoides</i> as a complementary therapeutic agent for neuroblastoma, warranting further in vivo and clinical investigations to assess its safety and efficacy.