MTH1 inhibitor amplifies the lethality of reactive oxygen species to tumor in photodynamic therapy
Although photodynamic therapy (PDT) has been clinically applied tumor hypoxia still greatly restricts the performance of this oxygen-dependent oncological treatment. The delivery of oxygen donors to tumor may produce excessive reactive oxygen species (ROS) and damage the peripheral tissues. Herein,...
| Main Authors: | , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2020
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/145423 |
| _version_ | 1826116224572981248 |
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| author | Zhao, Lingzhi Li, Junyao Su, Yaoquan Yang, Liqiang Chen, Liu Qiang, Lei Wang, Yajing Xiang, Huijing Tham, Phoebe Huijun Peng, Juanjuan Zhao, Yanli |
| author2 | School of Physical and Mathematical Sciences |
| author_facet | School of Physical and Mathematical Sciences Zhao, Lingzhi Li, Junyao Su, Yaoquan Yang, Liqiang Chen, Liu Qiang, Lei Wang, Yajing Xiang, Huijing Tham, Phoebe Huijun Peng, Juanjuan Zhao, Yanli |
| author_sort | Zhao, Lingzhi |
| collection | NTU |
| description | Although photodynamic therapy (PDT) has been clinically applied tumor hypoxia still greatly restricts the performance of this oxygen-dependent oncological treatment. The delivery of oxygen donors to tumor may produce excessive reactive oxygen species (ROS) and damage the peripheral tissues. Herein, we developed a strategy to solve the hypoxia issue by enhancing the lethality of ROS. Before PDT, the ROS-defensing system of the cancer cells was obstructed by an inhibitor to MTH1, which is a key for the remediation of ROS-caused DNA damage. As a result, both nuclei and mitochondrial DNA damages were increased, remarkably promoting cellular apoptosis. The therapeutic results demonstrated that the performance of PDT can be improved by the MTH1 inhibitor, leading to efficient cancer cell killing effect in the hypoxic tumor. This strategy makes better use of the limited oxygen, holding the promise to achieve satisfactory therapeutic effect by PDT without generating redundant cytotoxic ROS. |
| first_indexed | 2024-10-01T04:07:30Z |
| format | Journal Article |
| id | ntu-10356/145423 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:07:30Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1454232023-02-28T19:26:26Z MTH1 inhibitor amplifies the lethality of reactive oxygen species to tumor in photodynamic therapy Zhao, Lingzhi Li, Junyao Su, Yaoquan Yang, Liqiang Chen, Liu Qiang, Lei Wang, Yajing Xiang, Huijing Tham, Phoebe Huijun Peng, Juanjuan Zhao, Yanli School of Physical and Mathematical Sciences School of Materials Science and Engineering Science::Medicine Cell Death Diseases Although photodynamic therapy (PDT) has been clinically applied tumor hypoxia still greatly restricts the performance of this oxygen-dependent oncological treatment. The delivery of oxygen donors to tumor may produce excessive reactive oxygen species (ROS) and damage the peripheral tissues. Herein, we developed a strategy to solve the hypoxia issue by enhancing the lethality of ROS. Before PDT, the ROS-defensing system of the cancer cells was obstructed by an inhibitor to MTH1, which is a key for the remediation of ROS-caused DNA damage. As a result, both nuclei and mitochondrial DNA damages were increased, remarkably promoting cellular apoptosis. The therapeutic results demonstrated that the performance of PDT can be improved by the MTH1 inhibitor, leading to efficient cancer cell killing effect in the hypoxic tumor. This strategy makes better use of the limited oxygen, holding the promise to achieve satisfactory therapeutic effect by PDT without generating redundant cytotoxic ROS. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) Published version This research is supported by the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03) and the Singapore Agency for Science, Technology and Research (A*STAR) AME IRG grant (A1883c0005). This work is also supported by the National Science Foundation of China (81702998 and 81701766). 2020-12-21T07:24:52Z 2020-12-21T07:24:52Z 2020 Journal Article Zhao, L., Li, J., Su, Y., Yang, L., Chen, L., Qiang, L., . . . Zhao, Y. (2020). MTH1 inhibitor amplifies the lethality of reactive oxygen species to tumor in photodynamic therapy. Science Advances, 6(10), eaaz0575-. doi:10.1126/sciadv.aaz0575 2375-2548 https://hdl.handle.net/10356/145423 10.1126/sciadv.aaz0575 32181355 10 6 en NRF-NRFI2018-03 A1883c0005 Science Advances © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). application/pdf |
| spellingShingle | Science::Medicine Cell Death Diseases Zhao, Lingzhi Li, Junyao Su, Yaoquan Yang, Liqiang Chen, Liu Qiang, Lei Wang, Yajing Xiang, Huijing Tham, Phoebe Huijun Peng, Juanjuan Zhao, Yanli MTH1 inhibitor amplifies the lethality of reactive oxygen species to tumor in photodynamic therapy |
| title | MTH1 inhibitor amplifies the lethality of reactive oxygen species to tumor in photodynamic therapy |
| title_full | MTH1 inhibitor amplifies the lethality of reactive oxygen species to tumor in photodynamic therapy |
| title_fullStr | MTH1 inhibitor amplifies the lethality of reactive oxygen species to tumor in photodynamic therapy |
| title_full_unstemmed | MTH1 inhibitor amplifies the lethality of reactive oxygen species to tumor in photodynamic therapy |
| title_short | MTH1 inhibitor amplifies the lethality of reactive oxygen species to tumor in photodynamic therapy |
| title_sort | mth1 inhibitor amplifies the lethality of reactive oxygen species to tumor in photodynamic therapy |
| topic | Science::Medicine Cell Death Diseases |
| url | https://hdl.handle.net/10356/145423 |
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