Oridonin induces Mdm2‐p60 to promote p53‐mediated apoptosis and cell cycle arrest in neuroblastoma
Abstract 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...
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| Format: | Article |
| Language: | English |
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Wiley
2019-09-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.2393 |
| _version_ | 1818058664322269184 |
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| author | Han‐Qing Zhu Chao Zhang Zhu‐Ying Guo Jun‐Mei Yang Jia‐Hui Guo Chen Chen Qiang‐Hua Yao Feng Liu Quan‐Wu Zhang Feng‐Hou Gao |
| author_facet | Han‐Qing Zhu Chao Zhang Zhu‐Ying Guo Jun‐Mei Yang Jia‐Hui Guo Chen Chen Qiang‐Hua Yao Feng Liu Quan‐Wu Zhang Feng‐Hou Gao |
| author_sort | Han‐Qing Zhu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-10T13:04:13Z |
| format | Article |
| id | doaj.art-e762cfa2d4ef48b1a586f2a843f051e4 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-10T13:04:13Z |
| publishDate | 2019-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-e762cfa2d4ef48b1a586f2a843f051e42022-12-22T01:47:54ZengWileyCancer Medicine2045-76342019-09-018115313532610.1002/cam4.2393Oridonin induces Mdm2‐p60 to promote p53‐mediated apoptosis and cell cycle arrest in neuroblastomaHan‐Qing Zhu0Chao Zhang1Zhu‐Ying Guo2Jun‐Mei Yang3Jia‐Hui Guo4Chen Chen5Qiang‐Hua Yao6Feng Liu7Quan‐Wu Zhang8Feng‐Hou Gao9Department of Oncology, Shanghai 9th People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Geriatrics, Shanghai 9th People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Oncology, Shanghai 9th People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Clinical Laboratory Children's Hospital Affiliated to Zhengzhou University Zhengzhou ChinaDepartment of Oncology, Shanghai 9th People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Oncology, Shanghai 9th People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Pediatrics The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaDepartment of Oncology, Shanghai 9th People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Pathology Zhengzhou Central Hospital Affiliated to Zhengzhou University Zhengzhou ChinaDepartment of Oncology, Shanghai 9th People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaAbstract 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.https://doi.org/10.1002/cam4.2393apoptosiscell cycle arrestMdm2‐p60Oridoninp53ROS |
| spellingShingle | Han‐Qing Zhu Chao Zhang Zhu‐Ying Guo Jun‐Mei Yang Jia‐Hui Guo Chen Chen Qiang‐Hua Yao Feng Liu Quan‐Wu Zhang Feng‐Hou Gao Oridonin induces Mdm2‐p60 to promote p53‐mediated apoptosis and cell cycle arrest in neuroblastoma Cancer Medicine apoptosis cell cycle arrest Mdm2‐p60 Oridonin p53 ROS |
| title | Oridonin induces Mdm2‐p60 to promote p53‐mediated apoptosis and cell cycle arrest in neuroblastoma |
| title_full | Oridonin induces Mdm2‐p60 to promote p53‐mediated apoptosis and cell cycle arrest in neuroblastoma |
| title_fullStr | Oridonin induces Mdm2‐p60 to promote p53‐mediated apoptosis and cell cycle arrest in neuroblastoma |
| title_full_unstemmed | Oridonin induces Mdm2‐p60 to promote p53‐mediated apoptosis and cell cycle arrest in neuroblastoma |
| title_short | Oridonin induces Mdm2‐p60 to promote p53‐mediated apoptosis and cell cycle arrest in neuroblastoma |
| title_sort | oridonin induces mdm2 p60 to promote p53 mediated apoptosis and cell cycle arrest in neuroblastoma |
| topic | apoptosis cell cycle arrest Mdm2‐p60 Oridonin p53 ROS |
| url | https://doi.org/10.1002/cam4.2393 |
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