Table of contents

Volume 7, Issue 4, pp. 20 - 33, April 2023

Issue cover
Cover: This month in Cell Stress: Macrolide antibiotics and the integrated stress response. Image credit: public domain image by National Institutes of Health (NIH). Image modified by Cell Stress. The cover is published under the CC BY 4.0 license. Enlarge issue cover

Research Articles

Macrolide antibiotics activate the integrated stress response and promote tumor proliferation

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 and Qi Wu

page 20-33 | 10.15698/cst2023.04.278 | Full text | PDF | Abstract

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.

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