Macrolide antibiotics activate the integrated stress response and promote tumor proliferation
Macrolide antibiotics are widely used antibacterial agents that are associated with autophagy inhibition. This study aimed to investigate the association between macrolide antibi-otics and malignant tumors, as well as the effect on autophagy, reactive oxygen species (ROS) accumulation and integrated...
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| Format: | Article |
| Language: | English |
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Shared Science Publishers OG
2023-03-01
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| Series: | Cell Stress |
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| Online Access: | http://www.cell-stress.com/researcharticles/2023a-yu-cell-stress/ |
| _version_ | 1797865688474320896 |
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| author | Xin Yu Ai-Ling Tian Ping Wang Juanjuan Li Juan Wu Bei Li Zhou Liu Siqing Liu Zhijie Gao Si Sun Shengrong Sun Yi Tu Qi Wu |
| author_facet | Xin Yu Ai-Ling Tian Ping Wang Juanjuan Li Juan Wu Bei Li Zhou Liu Siqing Liu Zhijie Gao Si Sun Shengrong Sun Yi Tu Qi Wu |
| author_sort | Xin Yu |
| collection | DOAJ |
| description | Macrolide antibiotics are widely used antibacterial agents that are associated with autophagy inhibition. This study aimed to investigate the association between macrolide antibi-otics and malignant tumors, as well as the effect on autophagy, reactive oxygen species (ROS) accumulation and integrated stress response (ISR). The meta-analysis indicated a modestly higher risk of cancer in macrolide antibiotic ever-users com-pared to non-users. Further experiments showed that macro-lides block autophagic flux by inhibiting lysosomal acidification. Additionally, azithromycin, a representative macrolide antibi-otic, induced the accumulation of ROS, and stimulated the ISR and the activation of transcription factor EB (TFEB) and TFE3 in a ROS-dependent manner. Finally, animal experiments confirmed that azithromycin promoted tumor progression in vivo, which could be receded by N-acetylcysteine, an inhibitor of ROS and ISR. Overall, this study reveals the potential role of macrolide antibiotics in malignant progression and highlights the need for further investigation into their effects. |
| first_indexed | 2024-04-09T23:13:18Z |
| format | Article |
| id | doaj.art-9fa465f30f3148a785c8cd5ca98ecab8 |
| institution | Directory Open Access Journal |
| issn | 2523-0204 |
| language | English |
| last_indexed | 2024-04-09T23:13:18Z |
| publishDate | 2023-03-01 |
| publisher | Shared Science Publishers OG |
| record_format | Article |
| series | Cell Stress |
| spelling | doaj.art-9fa465f30f3148a785c8cd5ca98ecab82023-03-22T10:16:31ZengShared Science Publishers OGCell Stress2523-02042023-03-0174203310.15698/cst2023.04.278Macrolide antibiotics activate the integrated stress response and promote tumor proliferationXin Yu0Ai-Ling Tian1Ping Wang2Juanjuan Li3Juan Wu4Bei Li5Zhou Liu6Siqing Liu7Zhijie Gao8Si Sun9Shengrong Sun10Yi Tu11Qi Wu12Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China.Gustave Roussy Cancer Campus, Villejuif Cedex, France.Medical College, Anhui University of Science and Technology, Huainan, AnHui, P. R. China.Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China.Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China.Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China.Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China.Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China.Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China.Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China.Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China.Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China.Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, P. R. China.Macrolide antibiotics are widely used antibacterial agents that are associated with autophagy inhibition. This study aimed to investigate the association between macrolide antibi-otics and malignant tumors, as well as the effect on autophagy, reactive oxygen species (ROS) accumulation and integrated stress response (ISR). The meta-analysis indicated a modestly higher risk of cancer in macrolide antibiotic ever-users com-pared to non-users. Further experiments showed that macro-lides block autophagic flux by inhibiting lysosomal acidification. Additionally, azithromycin, a representative macrolide antibi-otic, induced the accumulation of ROS, and stimulated the ISR and the activation of transcription factor EB (TFEB) and TFE3 in a ROS-dependent manner. Finally, animal experiments confirmed that azithromycin promoted tumor progression in vivo, which could be receded by N-acetylcysteine, an inhibitor of ROS and ISR. Overall, this study reveals the potential role of macrolide antibiotics in malignant progression and highlights the need for further investigation into their effects.http://www.cell-stress.com/researcharticles/2023a-yu-cell-stress/macrolide antibioticazithromycinautophagyroser stresscancer |
| spellingShingle | Xin Yu Ai-Ling Tian Ping Wang Juanjuan Li Juan Wu Bei Li Zhou Liu Siqing Liu Zhijie Gao Si Sun Shengrong Sun Yi Tu Qi Wu Macrolide antibiotics activate the integrated stress response and promote tumor proliferation Cell Stress macrolide antibiotic azithromycin autophagy ros er stress cancer |
| title | Macrolide antibiotics activate the integrated stress response and promote tumor proliferation |
| title_full | Macrolide antibiotics activate the integrated stress response and promote tumor proliferation |
| title_fullStr | Macrolide antibiotics activate the integrated stress response and promote tumor proliferation |
| title_full_unstemmed | Macrolide antibiotics activate the integrated stress response and promote tumor proliferation |
| title_short | Macrolide antibiotics activate the integrated stress response and promote tumor proliferation |
| title_sort | macrolide antibiotics activate the integrated stress response and promote tumor proliferation |
| topic | macrolide antibiotic azithromycin autophagy ros er stress cancer |
| url | http://www.cell-stress.com/researcharticles/2023a-yu-cell-stress/ |
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