Polyphyllin D induces necroptosis in neuroblastoma cells (IMR-32 and LA-N-2) in mice

Abstract

Abstract Background We previously reported that polyphyllin D, the main component of the traditional herbal medicinal Paris polyphylla, exhibited anticancer effects in vitro against human neuroblastoma cells. The aim of this investigation was to examine in vivo antitumor effects of polyphyllin D. Methods Subcutaneous tumors were established in immune-deficient BALB/c nude mice using human neuroblastoma cell lines IMR-32 and LA-N-2. To evaluate the polyphyllin D activity, we used a mouse model of IMR-32 or LA-N-2 cell lines and analyzed subcutaneous tumors. Results Subcutaneous tumor models were successfully established in mice using two human neuroblastoma cell lines. In the subcutaneous tumor model, we found that polyphyllin D suppressed both the tumor volume and number of foci. We found that polyphyllin D induces the RIPK3 expression, while IMR-32 phosphorylates Ser358, a kinase domain that induces necroptosis, and LA-N-2 phosphorylates Ser358 and Tyr376, which promote necroptosis. Conclusion We developed a mouse model of subcutaneous tumors ofneuroblastoma and demonstrated for the first time that polyphyllin D has an antitumor effect on neuroblastoma. Polyphyllin D can cause necroptosis depending on the cell type. The new drug can be expected by investigating a method to selectively suppress cell death through the analysis of necroptosis.