Narciclasine reduces proliferation and migration of neuroblastoma cells and decreases FAK/PI3K pathway activation.

Neuroblastoma is a highly aggressive childhood malignancy originating from neural crest-derived cells. Narciclasine, an Amaryllidaceae-derived alkaloid isolated from plants such as Lycoris radiata, has been reported to exhibit various pharmacological activities; however, its effects in neuroblastoma remain poorly understood. In this study, we investigated the effects of narciclasine on SH-SY5Y neuroblastoma cells, focusing on proliferation, migration, apoptosis, DNA damage, and FAK/PI3K-associated signaling. Cell viability was evaluated using the CCK-8 assay; proliferation by Ki67 immunofluorescence staining; migration and colony formation by wound-healing and colony formation assays; apoptosis by TUNEL and cleaved caspase-3 immunofluorescence staining; DNA damage by COMET assay; and FAK/PI3K-related protein expression by immunohistochemistry and Western blot analysis. Treatment with 50 and 100 nM narciclasine significantly reduced SH-SY5Y cell viability while exhibiting comparatively lower cytotoxic effects in HUVEC cells under the tested conditions; therefore, these concentrations were selected for subsequent experiments. Narciclasine treatment also reduced cell proliferation, migration, and colony formation, while increasing apoptosis and DNA damage. Immunofluorescence analyses demonstrated decreased Ki67 expression and increased cleaved caspase-3 immunoreactivity in narciclasine-treated groups. In addition, immunohistochemical and Western blot analyses revealed reduced expression levels of FAK and PI3K following narciclasine treatment. Collectively, these findings suggest that narciclasine exerts anti-neuroblastoma effects associated with reduced proliferative and migratory activity, increased apoptotic response, and modulation of FAK/PI3K-associated signaling in SH-SY5Y cells. Further studies are needed to clarify the precise molecular basis and therapeutic relevance of these effects.