title: Polyphyllin D, a steroidal saponin in Paris polyphylla, induces apoptosis and necroptosis cell death of neuroblastoma cells.
abstract: OBJECTIVE
  Neuroblastoma is a refractory pediatric malignant solid tumor. The previous studies demonstrated that Polyphyllin D, the main constituent of Paris polyphylla, a traditional Chinese medicine, exerts an anti-tumor effect on many tumors. However, its effects against neuroblastomas are unclear.
  
  
  METHODS
  We examined the anti-tumor effect of polyphyllin D in human neuroblastoma using IMR-32 and LA-N-2 cells, which exhibit MYCN gene amplification, and NB-69 cells, which do not exhibit MYCN gene amplification.
  
  
  RESULTS
  All cell lines showed reduced cell viability in response to polyphyllin D treatment. No caspase-3/-7, -8, and -9 activity was observed in IMR-32 and LA-N-2 cells treated with polyphyllin D. In contrast, activation of caspase-3/-7, and -8 activity was observed in NB-69 cells. When polyphyllin D and specific inhibitors of RIPK3 involved in necroptosis were added to IMR-32 and LA-N-2 cell lines, polyphyllin D-induced cell death was inhibited.
  
  
  CONCLUSIONS
  Together, this indicates that the underlying mechanism of polyphyllin D-induced cell death in NB-69 cells is apoptosis, whereas the cell death of IMR-32 and LA-N-2 cells occurs by necroptosis. We continue research on this topic and look forward the discovery of a new therapeutic agent for neuroblastoma.
authors.affiliation: Department of Pediatric Surgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi, 470-1192, Japan. watanabe@fujita-hu.ac.jp.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of Pediatric Surgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Tatuya
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Pediatric Surgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Fujio
authors.initials: F
authors.lastname: Hara
authors.affiliation: Department of Pediatric Surgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Yasui
authors.affiliation: Department of Pediatric Surgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Uga
authors.affiliation: Department of Pediatric Surgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Atuki
authors.initials: A
authors.lastname: Naoe
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D019668:Liliaceae; D009336:Necrosis; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D008517:Phytotherapy; D012503:Saponins / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D012503:Saponins; C121203:polyphyllin D; D053148:Caspase 3; D004144:Diosgenin
keywords: Apoptosis; MYCN gene; Necroptosis; Neuroblastoma; Polyphyllin D