Oridonin induces Mdm2-p60 to promote p53-mediated apoptosis and cell cycle arrest in neuroblastoma. 2019

Han-Qing Zhu, and Chao Zhang, and Zhu-Ying Guo, and Jun-Mei Yang, and Jia-Hui Guo, and Chen Chen, and Qiang-Hua Yao, and Feng Liu, and Quan-Wu Zhang, and Feng-Hou Gao
Department of Oncology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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.

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009447 Neuroblastoma A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51) Neuroblastomas
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000972 Antineoplastic Agents, Phytogenic Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity. Antineoplastics, Botanical,Antineoplastics, Phytogenic,Agents, Phytogenic Antineoplastic,Botanical Antineoplastics,Phytogenic Antineoplastic Agents,Phytogenic Antineoplastics
D016159 Tumor Suppressor Protein p53 Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER. p53 Tumor Suppressor Protein,Cellular Tumor Antigen p53,Oncoprotein p53,TP53 Protein,TRP53 Protein,p53 Antigen,pp53 Phosphoprotein,Phosphoprotein, pp53
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D017382 Reactive Oxygen Species Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS. Active Oxygen Species,Oxygen Radical,Oxygen Radicals,Pro-Oxidant,Reactive Oxygen Intermediates,Active Oxygen,Oxygen Species, Reactive,Pro-Oxidants,Oxygen, Active,Pro Oxidant,Pro Oxidants,Radical, Oxygen

Related Publications

Han-Qing Zhu, and Chao Zhang, and Zhu-Ying Guo, and Jun-Mei Yang, and Jia-Hui Guo, and Chen Chen, and Qiang-Hua Yao, and Feng Liu, and Quan-Wu Zhang, and Feng-Hou Gao
April 1997, Leukemia,
Han-Qing Zhu, and Chao Zhang, and Zhu-Ying Guo, and Jun-Mei Yang, and Jia-Hui Guo, and Chen Chen, and Qiang-Hua Yao, and Feng Liu, and Quan-Wu Zhang, and Feng-Hou Gao
December 2016, Oncotarget,
Han-Qing Zhu, and Chao Zhang, and Zhu-Ying Guo, and Jun-Mei Yang, and Jia-Hui Guo, and Chen Chen, and Qiang-Hua Yao, and Feng Liu, and Quan-Wu Zhang, and Feng-Hou Gao
September 2010, Oncology reports,
Han-Qing Zhu, and Chao Zhang, and Zhu-Ying Guo, and Jun-Mei Yang, and Jia-Hui Guo, and Chen Chen, and Qiang-Hua Yao, and Feng Liu, and Quan-Wu Zhang, and Feng-Hou Gao
June 2021, Molecular medicine reports,
Han-Qing Zhu, and Chao Zhang, and Zhu-Ying Guo, and Jun-Mei Yang, and Jia-Hui Guo, and Chen Chen, and Qiang-Hua Yao, and Feng Liu, and Quan-Wu Zhang, and Feng-Hou Gao
May 2006, Cancer biology & therapy,
Han-Qing Zhu, and Chao Zhang, and Zhu-Ying Guo, and Jun-Mei Yang, and Jia-Hui Guo, and Chen Chen, and Qiang-Hua Yao, and Feng Liu, and Quan-Wu Zhang, and Feng-Hou Gao
March 2007, International journal of molecular medicine,
Han-Qing Zhu, and Chao Zhang, and Zhu-Ying Guo, and Jun-Mei Yang, and Jia-Hui Guo, and Chen Chen, and Qiang-Hua Yao, and Feng Liu, and Quan-Wu Zhang, and Feng-Hou Gao
October 2020, Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan,
Han-Qing Zhu, and Chao Zhang, and Zhu-Ying Guo, and Jun-Mei Yang, and Jia-Hui Guo, and Chen Chen, and Qiang-Hua Yao, and Feng Liu, and Quan-Wu Zhang, and Feng-Hou Gao
March 2000, Oncogene,
Han-Qing Zhu, and Chao Zhang, and Zhu-Ying Guo, and Jun-Mei Yang, and Jia-Hui Guo, and Chen Chen, and Qiang-Hua Yao, and Feng Liu, and Quan-Wu Zhang, and Feng-Hou Gao
June 2020, Oncogene,
Han-Qing Zhu, and Chao Zhang, and Zhu-Ying Guo, and Jun-Mei Yang, and Jia-Hui Guo, and Chen Chen, and Qiang-Hua Yao, and Feng Liu, and Quan-Wu Zhang, and Feng-Hou Gao
November 2019, Molecules (Basel, Switzerland),
Copied contents to your clipboard!