Boanmycin induces apoptosis and overcomes venetoclax resistance in acute myeloid leukemia

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-07-16 DOI:10.1515/oncologie-2024-0140

Jin-Xing Wang, Peng-Wei Zhang, Luo-Wei Yuan, Jian Jiang, Xiao-Hui Cheng, Ju-Heng Li, Mei-Qin Tang, Jiao-Yang Fan, Wei Zhu, Yong Lei, Faqing Tian

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Abstract

This study aimed to investigate the efficacy of boanmycin, a clinical drug used for head and neck cancers, in the treatment of acute myeloid leukemia (AML), particularly in venetoclax-resistant AML cells. The cell viability assay was conducted to measure the inhibitory effects of boanmycin on the AML cell lines and patient primary cells using the CCK8 reagent. The colony formation assay was performed to evaluate the colony formation ability of HL60 and venetoclax-resistant HL60 (HL60-res) cells with or without boanmycin treatment. Flow cytometry was performed to detect cell apoptosis level, and Western blot was used to assess changes in apoptosis-related proteins. Our findings reveal that boanmycin significantly inhibits AML cell proliferation and colony formation, and induces apoptosis. Importantly, boanmycin exhibits substantial inhibitory effects on venetoclax-resistant cells, and suppresses the proliferation of peripheral blood mononuclear cells (PBMCs) or bone marrow mononuclear cells (BMMCs) derived from newly diagnosed and relapsed AML patients. Boanmycin may overcome venetoclax resistance and offer therapeutic benefits for patients with venetoclax-resistant AML.

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博安霉素能诱导急性髓性白血病患者的细胞凋亡并克服 Venetoclax 的耐药性

本研究旨在探讨用于治疗头颈部癌症的临床药物博安霉素在治疗急性髓性白血病（AML）中的疗效，尤其是对耐药AML细胞的疗效。使用 CCK8 试剂进行了细胞活力测定，以测量博安霉素对急性髓性白血病细胞系和患者原代细胞的抑制作用。集落形成试验是为了评估 HL60 细胞和耐 Venetoclax 的 HL60（HL60-res）细胞在博安霉素处理或不处理的情况下的集落形成能力。流式细胞术检测细胞凋亡水平，Western印迹评估细胞凋亡相关蛋白的变化。我们的研究结果表明，博安霉素能明显抑制急性髓细胞白血病细胞的增殖和集落形成，并诱导细胞凋亡。重要的是，博安霉素对文尼考昔（venetoclax）耐药细胞有明显的抑制作用，并能抑制来自新诊断和复发急性髓细胞性白血病患者的外周血单核细胞（PBMCs）或骨髓单核细胞（BMMCs）的增殖。博安霉素可克服 Venetoclax 耐药性，为 Venetoclax 耐药性急性髓细胞性白血病患者带来治疗益处。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.