Macrolide antibiotics activate the integrated stress response and promote tumor proliferation.

Autor:	Yu X; Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China., Tian AL; Gustave Roussy Cancer Campus, Villejuif Cedex, France.; Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France.; Centre de Recherche des Cordeliers, INSERM U1138, Équipe Labellisée - Ligue Nationale contre le Cancer, Université Paris Cité, Sorbonne Université, Paris, France.; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France., Wang P; Medical College, Anhui University of Science and Technology, Huainan, AnHui, P. R. China., Li J; Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China., Wu J; Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China., Li B; Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China., Liu Z; Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China., Liu S; Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China., Gao Z; Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China., Sun S; Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China., Sun S; Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China., Tu Y; Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China., Wu Q; Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, P. R. China.
Jazyk:	angličtina
Zdroj:	Cell stress [Cell Stress] 2023 Mar 21; Vol. 7 (4), pp. 20-33. Date of Electronic Publication: 2023 Mar 21 (Print Publication: 2023).
DOI:	10.15698/cst2023.04.278
Abstrakt:	Macrolide antibiotics are widely used antibacterial agents that are associated with autophagy inhibition. This study aimed to investigate the association between macrolide antibiotics 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 compared to non-users. Further experiments showed that macrolides block autophagic flux by inhibiting lysosomal acidification. Additionally, azithromycin, a representative macrolide antibiotic, 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. Competing Interests: Conflict of Interest: All the authors agree to the submission and consent for publication this paper. The authors have declared that no competing interest exists. (Copyright: © 2023 Yu et al.)
Databáze:	MEDLINE
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