Macrolide antibiotics activate the integrated stress response and promote tumor proliferation

Autor: 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
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Stress, Vol 7, Iss 4, Pp 20-33 (2023)
Druh dokumentu: article
ISSN: 2523-0204
DOI: 10.15698/cst2023.04.278
Popis: 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.
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