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

IF 4.1 Q2 CELL BIOLOGY

Cell Stress Pub Date : 2023-04-01 DOI:10.15698/cst2023.04.278

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

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引用次数: 1

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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大环内酯类抗生素激活综合应激反应，促进肿瘤增殖。

大环内酯类抗生素是广泛使用的抗菌药物，与自噬抑制有关。本研究旨在探讨大环内酯类抗生素与恶性肿瘤的关系，以及对自噬、活性氧(ROS)积累和综合应激反应(ISR)的影响。荟萃分析表明，与不使用大环内酯类抗生素的人相比，曾经使用大环内酯类抗生素的人患癌症的风险略高。进一步的实验表明大环内酯类通过抑制溶酶体酸化来阻断自噬通量。此外，阿奇霉素作为大环内酯类抗生素的代表，诱导ROS的积累，并以ROS依赖的方式刺激ISR和转录因子EB (TFEB)和TFE3的激活。最后，动物实验证实了阿奇霉素在体内促进肿瘤进展，这可以通过抑制ROS和ISR的n -乙酰半胱氨酸来减缓。总的来说，这项研究揭示了大环内酯类抗生素在恶性进展中的潜在作用，并强调了进一步研究其作用的必要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Stress Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (miscellaneous)

CiteScore

13.50

自引率

0.00%

发文量

审稿时长

15 weeks

期刊介绍： Cell Stress is an open-access, peer-reviewed journal that is dedicated to publishing highly relevant research in the field of cellular pathology. The journal focuses on advancing our understanding of the molecular, mechanistic, phenotypic, and other critical aspects that underpin cellular dysfunction and disease. It specifically aims to foster cell biology research that is applicable to a range of significant human diseases, including neurodegenerative disorders, myopathies, mitochondriopathies, infectious diseases, cancer, and pathological aging. The scope of Cell Stress is broad, welcoming submissions that represent a spectrum of research from fundamental to translational and clinical studies. The journal is a valuable resource for scientists, educators, and policymakers worldwide, as well as for any individual with an interest in cellular pathology. It serves as a platform for the dissemination of research findings that are instrumental in the investigation, classification, diagnosis, and therapeutic management of major diseases. By being open-access, Cell Stress ensures that its content is freely available to a global audience, thereby promoting international scientific collaboration and accelerating the exchange of knowledge within the research community.