Elafibranor emerged as a potential chemotherapeutic drug for non-muscle invasive bladder cancer
Intravesical infusion of chemotherapeutics is highly recommended by several clinical guidelines for treating nonmuscle invasive bladder cancer (NMIBC). However, cytotoxic chemotherapeutics can cause a series of side effects, which greatly limits their application. Herein, a starvation therapy strate...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Cell Insight |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S277289272400004X |
| _version_ | 1797339181166362624 |
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| author | Wang Wang Danni Shan Guanyi Wang Xiongmin Mao Wenjie You Xiaolong Wang Zijian Wang |
| author_facet | Wang Wang Danni Shan Guanyi Wang Xiongmin Mao Wenjie You Xiaolong Wang Zijian Wang |
| author_sort | Wang Wang |
| collection | DOAJ |
| description | Intravesical infusion of chemotherapeutics is highly recommended by several clinical guidelines for treating nonmuscle invasive bladder cancer (NMIBC). However, cytotoxic chemotherapeutics can cause a series of side effects, which greatly limits their application. Herein, a starvation therapy strategy was proposed, and elafibranor (ELA) was validated as a safe chemotherapeutic for NMIBC. The results showed that 20 μM ELA was sufficient to inhibit the proliferation and migration of bladder cancer cells and increase the level of intracellular reactive oxygen species (ROS). Furthermore, 2 mg/kg ELA treatment blocked the growth of primary tumors in an immunodeficient model by inhibiting proliferation and inducing apoptosis and improved the survival time of immunocompetent model mice. ELA treatment up to 10 mg/kg met the general safety requirements. We also established a patient-derived conditional reprogramming cell (CRC) model to assess the clinical translational potential of ELA. The antitumor effect and antitumor specificity of ELA treatment were confirmed. This work not only identified a promising chemotherapeutic for NMIBC but also provided a potential methodological system for drug discovery. |
| first_indexed | 2024-03-08T09:42:14Z |
| format | Article |
| id | doaj.art-e75a59b16bce4a8894ec6fe3d364c666 |
| institution | Directory Open Access Journal |
| issn | 2772-8927 |
| language | English |
| last_indexed | 2024-03-08T09:42:14Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
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| series | Cell Insight |
| spelling | doaj.art-e75a59b16bce4a8894ec6fe3d364c6662024-01-30T04:19:19ZengElsevierCell Insight2772-89272024-02-0131100149Elafibranor emerged as a potential chemotherapeutic drug for non-muscle invasive bladder cancerWang Wang0Danni Shan1Guanyi Wang2Xiongmin Mao3Wenjie You4Xiaolong Wang5Zijian Wang6Department of Urology, Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, ChinaDepartment of Urology, Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, ChinaDepartment of Urology, Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, ChinaDepartment of Urology, Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, ChinaOrthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China; Corresponding author.Department of Urology, Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China; Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA; Corresponding author. Department of Urology, Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.Department of Urology, Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China; Department of Biomedical Engineering and Hubei Province Key Laboratory of Allergy and Immune Related Disease, Taikang Medical School (School of Basic Medicine Sciences), Wuhan University, Wuhan, 430071, China; Corresponding author. Department of Urology, Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.Intravesical infusion of chemotherapeutics is highly recommended by several clinical guidelines for treating nonmuscle invasive bladder cancer (NMIBC). However, cytotoxic chemotherapeutics can cause a series of side effects, which greatly limits their application. Herein, a starvation therapy strategy was proposed, and elafibranor (ELA) was validated as a safe chemotherapeutic for NMIBC. The results showed that 20 μM ELA was sufficient to inhibit the proliferation and migration of bladder cancer cells and increase the level of intracellular reactive oxygen species (ROS). Furthermore, 2 mg/kg ELA treatment blocked the growth of primary tumors in an immunodeficient model by inhibiting proliferation and inducing apoptosis and improved the survival time of immunocompetent model mice. ELA treatment up to 10 mg/kg met the general safety requirements. We also established a patient-derived conditional reprogramming cell (CRC) model to assess the clinical translational potential of ELA. The antitumor effect and antitumor specificity of ELA treatment were confirmed. This work not only identified a promising chemotherapeutic for NMIBC but also provided a potential methodological system for drug discovery.http://www.sciencedirect.com/science/article/pii/S277289272400004XElafibranorBladder cancerConditional reprogramming cellDrug developmentPreclinical study |
| spellingShingle | Wang Wang Danni Shan Guanyi Wang Xiongmin Mao Wenjie You Xiaolong Wang Zijian Wang Elafibranor emerged as a potential chemotherapeutic drug for non-muscle invasive bladder cancer Cell Insight Elafibranor Bladder cancer Conditional reprogramming cell Drug development Preclinical study |
| title | Elafibranor emerged as a potential chemotherapeutic drug for non-muscle invasive bladder cancer |
| title_full | Elafibranor emerged as a potential chemotherapeutic drug for non-muscle invasive bladder cancer |
| title_fullStr | Elafibranor emerged as a potential chemotherapeutic drug for non-muscle invasive bladder cancer |
| title_full_unstemmed | Elafibranor emerged as a potential chemotherapeutic drug for non-muscle invasive bladder cancer |
| title_short | Elafibranor emerged as a potential chemotherapeutic drug for non-muscle invasive bladder cancer |
| title_sort | elafibranor emerged as a potential chemotherapeutic drug for non muscle invasive bladder cancer |
| topic | Elafibranor Bladder cancer Conditional reprogramming cell Drug development Preclinical study |
| url | http://www.sciencedirect.com/science/article/pii/S277289272400004X |
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