Neuropathiazol induces neuronal-like differentiation in neuroblastoma cells via upregulation of PEG5

Abstract

Differentiation therapy is emerging as a promising strategy for treating neuroblastoma. However, the effects of neuropathiazol, a small molecule known to induce neuronal differentiation, have not been explored in neuroblastoma. Neuroblastoma cell lines were used to investigate the effects of neuropathiazol and retinoic acid on cell morphology, proliferation, and invasion in vitro. In vivo, neuroblastoma cells were implanted in nude mice to assess neuropathiazol’s therapeutic potential. Silver staining and markers of mature neurons were employed to evaluate neuropathiazol’s ability to promote neuronal differentiation. Neuropathiazol significantly inhibited the proliferation and invasion of neuroblastoma cells in vitro. It also enhanced synaptic growth and increased the expression of mature neuron markers more effectively than retinoic acid. Neuropathiazol treatment upregulated PEG5 expression, suggesting its role in promoting neuronal differentiation. Silencing PEG5 reversed these differentiation effects, reducing neuronal features. In vivo, neuropathiazol suppressed tumor growth and induced neuron-like differentiation in tumor tissues. However, its efficacy was diminished when PEG5 was knocked down. Additionally, neuropathiazol synergized with cyclophosphamide, enhancing its anti-neuroblastoma effects. Neuropathiazol induces neuroblastoma differentiation, partly through PEG5 upregulation. As a promising differentiating agent for neuroblastoma, the combination of neuropathiazol and cyclophosphamide offers a potential treatment strategy for the disease.