Combined treatment of disulfiram with PARP inhibitors suppresses ovarian cancer
IntroductionDue to the difficulty of early diagnosis, nearly 70% of ovarian cancer patients are first diagnosed at an advanced stage. Thus, improving current treatment strategies is of great significance for ovarian cancer patients. Fast-developing poly (ADP-ribose) polymerases inhibitors (PARPis) h...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1154073/full |
| _version_ | 1797845008485711872 |
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| author | Bin Tang Min Wu Lin Zhang Shuyi Jian Shiyi Lv Tongyuan Lin Shuangshuang Zhu Layang Liu Yixue Wang Zhengfang Yi Feiyun Jiang |
| author_facet | Bin Tang Min Wu Lin Zhang Shuyi Jian Shiyi Lv Tongyuan Lin Shuangshuang Zhu Layang Liu Yixue Wang Zhengfang Yi Feiyun Jiang |
| author_sort | Bin Tang |
| collection | DOAJ |
| description | IntroductionDue to the difficulty of early diagnosis, nearly 70% of ovarian cancer patients are first diagnosed at an advanced stage. Thus, improving current treatment strategies is of great significance for ovarian cancer patients. Fast-developing poly (ADP-ribose) polymerases inhibitors (PARPis) have been beneficial in the treatment of ovarian cancer at different stages of the disease, but PARPis have serious side effects and can result in drug resistance. Using PARPis in combination with other drug therapies could improve the efficacy of PRAPis.In this study, we identified Disulfiram as a potential therapeutic candidate through drug screening and tested its use in combination with PARPis.MethodsCytotoxicity tests and colony formation experiments showed that the combination of Disulfiram and PARPis decreased the viability of ovarian cancer cellsResultsThe combination of PARPis with Disulfiram also significantly increased the expression of DNA damage index gH2AX and induced more PARP cleavage. In addition, Disulfiram inhibited the expression of genes associated with the DNA damage repair pathway, indicating that Disulfiram functions through the DNA repair pathway.DiscussionBased on these findings, we propose that Disulfiram reinforces PARPis activity in ovarian cancer cells by improving drug sensitivity. The combined use of Disulfiram and PARPis provides a novel treatment strategy for patients with ovarian cancer. |
| first_indexed | 2024-04-09T17:31:38Z |
| format | Article |
| id | doaj.art-91cc01bbe89a4cd7bf0fa107433f194e |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-09T17:31:38Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-91cc01bbe89a4cd7bf0fa107433f194e2023-04-18T05:02:57ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-04-011310.3389/fonc.2023.11540731154073Combined treatment of disulfiram with PARP inhibitors suppresses ovarian cancerBin Tang0Min Wu1Lin Zhang2Shuyi Jian3Shiyi Lv4Tongyuan Lin5Shuangshuang Zhu6Layang Liu7Yixue Wang8Zhengfang Yi9Feiyun Jiang10Department of Gynecology, East China Normal University Wuhu Affiliated Hospital (The Second People’s Hospital of Wuhu City), Wuhu, ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, ChinaDepartment of Gynecology, East China Normal University Wuhu Affiliated Hospital (The Second People’s Hospital of Wuhu City), Wuhu, ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, ChinaDepartment of Gynecology, East China Normal University Wuhu Affiliated Hospital (The Second People’s Hospital of Wuhu City), Wuhu, ChinaIntroductionDue to the difficulty of early diagnosis, nearly 70% of ovarian cancer patients are first diagnosed at an advanced stage. Thus, improving current treatment strategies is of great significance for ovarian cancer patients. Fast-developing poly (ADP-ribose) polymerases inhibitors (PARPis) have been beneficial in the treatment of ovarian cancer at different stages of the disease, but PARPis have serious side effects and can result in drug resistance. Using PARPis in combination with other drug therapies could improve the efficacy of PRAPis.In this study, we identified Disulfiram as a potential therapeutic candidate through drug screening and tested its use in combination with PARPis.MethodsCytotoxicity tests and colony formation experiments showed that the combination of Disulfiram and PARPis decreased the viability of ovarian cancer cellsResultsThe combination of PARPis with Disulfiram also significantly increased the expression of DNA damage index gH2AX and induced more PARP cleavage. In addition, Disulfiram inhibited the expression of genes associated with the DNA damage repair pathway, indicating that Disulfiram functions through the DNA repair pathway.DiscussionBased on these findings, we propose that Disulfiram reinforces PARPis activity in ovarian cancer cells by improving drug sensitivity. The combined use of Disulfiram and PARPis provides a novel treatment strategy for patients with ovarian cancer.https://www.frontiersin.org/articles/10.3389/fonc.2023.1154073/fullpoly (ADP-ribose) polymerase inhibitorsovarian cancerdrug combinationdisulfiramDNA damage repair |
| spellingShingle | Bin Tang Min Wu Lin Zhang Shuyi Jian Shiyi Lv Tongyuan Lin Shuangshuang Zhu Layang Liu Yixue Wang Zhengfang Yi Feiyun Jiang Combined treatment of disulfiram with PARP inhibitors suppresses ovarian cancer Frontiers in Oncology poly (ADP-ribose) polymerase inhibitors ovarian cancer drug combination disulfiram DNA damage repair |
| title | Combined treatment of disulfiram with PARP inhibitors suppresses ovarian cancer |
| title_full | Combined treatment of disulfiram with PARP inhibitors suppresses ovarian cancer |
| title_fullStr | Combined treatment of disulfiram with PARP inhibitors suppresses ovarian cancer |
| title_full_unstemmed | Combined treatment of disulfiram with PARP inhibitors suppresses ovarian cancer |
| title_short | Combined treatment of disulfiram with PARP inhibitors suppresses ovarian cancer |
| title_sort | combined treatment of disulfiram with parp inhibitors suppresses ovarian cancer |
| topic | poly (ADP-ribose) polymerase inhibitors ovarian cancer drug combination disulfiram DNA damage repair |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1154073/full |
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