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Oridonin induces Mdm2-p60 to promote p53-mediated apoptosis and cell cycle arrest in neuroblastoma.
Zhu, Han-Qing; Zhang, Chao; Guo, Zhu-Ying; Yang, Jun-Mei; Guo, Jia-Hui; Chen, Chen; Yao, Qiang-Hua; Liu, Feng; Zhang, Quan-Wu; Gao, Feng-Hou.
Afiliación
  • Zhu HQ; Department of Oncology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zhang C; Department of Geriatrics, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Guo ZY; Department of Oncology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Yang JM; Department of Clinical Laboratory, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
  • Guo JH; Department of Oncology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Chen C; Department of Oncology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Yao QH; Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • Liu F; Department of Oncology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zhang QW; Department of Pathology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
  • Gao FH; Department of Oncology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Cancer Med ; 8(11): 5313-5326, 2019 Sep.
Article en En | MEDLINE | ID: mdl-31339234
Oridonin could induce NB (neuroblastoma) cells growth inhibition by inducing apoptosis and cell cycle arrest, and the molecular mechanisms behind the effects deserve to be further explored. Here, oridonin was confirmed to cause the reactivation of p53 (cellular tumor antigen p53) to promote the expression of a series of apoptosis- and cell cycle arrest-related proteins for the biological effects. During the process, oridonin relied on the caspase activation to cleave p53-induced Mdm2 (E3 ubiquitin-protein ligase Mdm2) to generate Mdm2-p60. The generation of Mdm2-p60 stabilized p53, and resulted in p53 accumulation for p53 continuous activation. In our research, it was also found that the reactivation of p53 induced by oridonin was closely related with the generation of ROS (reactive oxygen species). Taken together, these findings explain that oridonin exerts its anticancer activity partially by targeting the Mdm2-p53 axis in NB cells, which lay an experimental base for future research of exploring the effects and molecular mechanisms of oridonin.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína p53 Supresora de Tumor / Apoptosis / Diterpenos de Tipo Kaurano / Proteínas Proto-Oncogénicas c-mdm2 / Puntos de Control del Ciclo Celular / Antineoplásicos Fitogénicos Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Cancer Med Año: 2019 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína p53 Supresora de Tumor / Apoptosis / Diterpenos de Tipo Kaurano / Proteínas Proto-Oncogénicas c-mdm2 / Puntos de Control del Ciclo Celular / Antineoplásicos Fitogénicos Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Cancer Med Año: 2019 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos