Periodic Oxaliplatin Administration in Synergy with PER2‐Mediated PCNA Transcription Repression Promotes Chronochemotherapeutic Efficacy of OSCC
Abstract Developing chemotherapeutic resistance affects clinical outcomes of oxaliplatin treatment on various types of cancer. Thus, it is imperative to explore alternative therapeutic strategies to improve the efficacy of oxaliplatin. Here, it is shown that circadian regulator period 2 (PER2) can p...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-11-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.201900667 |
| _version_ | 1818965957934055424 |
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| author | Qingming Tang Mengru Xie Shaoling Yu Xin Zhou Yanling Xie Guangjin Chen Fengyuan Guo Lili Chen |
| author_facet | Qingming Tang Mengru Xie Shaoling Yu Xin Zhou Yanling Xie Guangjin Chen Fengyuan Guo Lili Chen |
| author_sort | Qingming Tang |
| collection | DOAJ |
| description | Abstract Developing chemotherapeutic resistance affects clinical outcomes of oxaliplatin treatment on various types of cancer. Thus, it is imperative to explore alternative therapeutic strategies to improve the efficacy of oxaliplatin. Here, it is shown that circadian regulator period 2 (PER2) can potentiate the cytotoxicity of oxaliplatin and boost cell apoptosis by inhibiting DNA adducts repair in human oral squamous cell carcinoma (OSCC) cells. The circadian timing system is closely involved in controling the activity of DNA adducts repair and gives it a 24 h rhythm. The mechanistic dissection clarifies that PER2 can periodically suppress proliferating cell nuclear antigen (PCNA) transcription by pulling down circadian locomotor output cycles kaput–brain and muscle arnt‐like 1 heterodimer from PCNA promoter in a CRY1/2‐dependent manner, which subsequently impedes oxaliplatin‐induced DNA adducts repair. Similarly, PER2 is capable of improving the efficacy of classical DNA‐damaging chemotherapeutic agents. The tumor‐bearing mouse model displays PER2 can be deployed as an oxaliplatin administration timing biomarker. In summary, it is believed that the chronochemotherapeutic strategy matching PER2 expression rhythm can efficiently improve the oxaliplatin efficacy of OSCC. |
| first_indexed | 2024-12-20T13:25:16Z |
| format | Article |
| id | doaj.art-dddbfc03a2174221a2a3316de57e87ff |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-20T13:25:16Z |
| publishDate | 2019-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-dddbfc03a2174221a2a3316de57e87ff2022-12-21T19:39:17ZengWileyAdvanced Science2198-38442019-11-01621n/an/a10.1002/advs.201900667Periodic Oxaliplatin Administration in Synergy with PER2‐Mediated PCNA Transcription Repression Promotes Chronochemotherapeutic Efficacy of OSCCQingming Tang0Mengru Xie1Shaoling Yu2Xin Zhou3Yanling Xie4Guangjin Chen5Fengyuan Guo6Lili Chen7Department of Stomatology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Stomatology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Stomatology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Stomatology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Stomatology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Stomatology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Stomatology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Stomatology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaAbstract Developing chemotherapeutic resistance affects clinical outcomes of oxaliplatin treatment on various types of cancer. Thus, it is imperative to explore alternative therapeutic strategies to improve the efficacy of oxaliplatin. Here, it is shown that circadian regulator period 2 (PER2) can potentiate the cytotoxicity of oxaliplatin and boost cell apoptosis by inhibiting DNA adducts repair in human oral squamous cell carcinoma (OSCC) cells. The circadian timing system is closely involved in controling the activity of DNA adducts repair and gives it a 24 h rhythm. The mechanistic dissection clarifies that PER2 can periodically suppress proliferating cell nuclear antigen (PCNA) transcription by pulling down circadian locomotor output cycles kaput–brain and muscle arnt‐like 1 heterodimer from PCNA promoter in a CRY1/2‐dependent manner, which subsequently impedes oxaliplatin‐induced DNA adducts repair. Similarly, PER2 is capable of improving the efficacy of classical DNA‐damaging chemotherapeutic agents. The tumor‐bearing mouse model displays PER2 can be deployed as an oxaliplatin administration timing biomarker. In summary, it is believed that the chronochemotherapeutic strategy matching PER2 expression rhythm can efficiently improve the oxaliplatin efficacy of OSCC.https://doi.org/10.1002/advs.201900667chronochemotherapeutic strategycircadian clock genesDNA‐damaging repairoral squamous cell carcinomaoxaliplatin |
| spellingShingle | Qingming Tang Mengru Xie Shaoling Yu Xin Zhou Yanling Xie Guangjin Chen Fengyuan Guo Lili Chen Periodic Oxaliplatin Administration in Synergy with PER2‐Mediated PCNA Transcription Repression Promotes Chronochemotherapeutic Efficacy of OSCC Advanced Science chronochemotherapeutic strategy circadian clock genes DNA‐damaging repair oral squamous cell carcinoma oxaliplatin |
| title | Periodic Oxaliplatin Administration in Synergy with PER2‐Mediated PCNA Transcription Repression Promotes Chronochemotherapeutic Efficacy of OSCC |
| title_full | Periodic Oxaliplatin Administration in Synergy with PER2‐Mediated PCNA Transcription Repression Promotes Chronochemotherapeutic Efficacy of OSCC |
| title_fullStr | Periodic Oxaliplatin Administration in Synergy with PER2‐Mediated PCNA Transcription Repression Promotes Chronochemotherapeutic Efficacy of OSCC |
| title_full_unstemmed | Periodic Oxaliplatin Administration in Synergy with PER2‐Mediated PCNA Transcription Repression Promotes Chronochemotherapeutic Efficacy of OSCC |
| title_short | Periodic Oxaliplatin Administration in Synergy with PER2‐Mediated PCNA Transcription Repression Promotes Chronochemotherapeutic Efficacy of OSCC |
| title_sort | periodic oxaliplatin administration in synergy with per2 mediated pcna transcription repression promotes chronochemotherapeutic efficacy of oscc |
| topic | chronochemotherapeutic strategy circadian clock genes DNA‐damaging repair oral squamous cell carcinoma oxaliplatin |
| url | https://doi.org/10.1002/advs.201900667 |
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