Aspirin-Inspired 6-O-Carboxymethyl-N-Acetylglucosamine: A potent antitumor agent with enhanced efficacy

IF 8.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Apoptosis Pub Date : 2025-07-05 DOI:10.1007/s10495-025-02139-4

Ziwen Qiao, Guangmin Zhang, Xin Chen, Yuefa Zhang, Sudan Zhang, Xiuheng Qin, Ammara Sohail, Xiaohui Xu, Jiane Liu, Baoqin Han, Daijie Wang, Xiangyan Zhang, Zheng Wang

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引用次数: 0

Abstract

Aspirin, widely recognized for its anti-inflammatory and cardioprotective effects, has also shown potential as a cancer therapeutic. However, its clinical application is hindered by severe adverse effects. Here, we explore 6-O-Carboxymethyl-N-Acetylglucosamine (CM-NAG) a novel derivative of N-acetylglucosamine, designed to mimic the structural and functional properties of aspirin. CM-NAG significantly inhibits the viability of both colorectal and pancreatic cancer cells. In colorectal cancer cells, CM-NAG also suppressed migration and invasion and induced apoptosis more effectively than aspirin. Mechanistically, CM-NAG upregulated phosphoenolpyruvate carboxykinase 2 (PCK2), a key regulator of gluconeogenesis in colorectal cancer cells. In a xenograft model, CM-NAG reduced tumor size and improved histopathological outcomes, while showing no significant toxicity in major organs. The expression of PCK2 in CRC tissues was significantly lower than in cancer-adjacent tissues, according immunohistochemistry analysis. Clinical analysis revealed high PCK2 expression in colorectal cancer tissues correlates with better disease-free survival, supporting PCK2 as a promising therapeutic target. These findings suggest that CM-NAG may represent a next-generation antitumor agent with enhanced efficacy and safety compared to aspirin, offering new prospects for cancer treatment.

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阿司匹林激发的6- o -羧甲基- n-乙酰氨基葡萄糖：一种有效的抗肿瘤药物。

阿司匹林因其抗炎和保护心脏的作用而被广泛认可，它也显示出治疗癌症的潜力。但其不良反应严重，阻碍了其临床应用。在这里，我们研究了6- o -羧基甲基- n -乙酰氨基葡萄糖胺（CM-NAG），一种新型的n -乙酰氨基葡萄糖胺衍生物，旨在模拟阿司匹林的结构和功能特性。CM-NAG显著抑制结直肠癌和胰腺癌细胞的活力。在结直肠癌细胞中，CM-NAG也比阿司匹林更有效地抑制迁移、侵袭和诱导凋亡。在机制上，CM-NAG上调磷酸烯醇丙酮酸羧激酶2 (PCK2)，这是结直肠癌细胞糖异生的关键调节因子。在异种移植模型中，CM-NAG缩小了肿瘤大小，改善了组织病理学结果，同时对主要器官没有明显的毒性。免疫组化分析显示，PCK2在结直肠癌组织中的表达明显低于癌旁组织。临床分析显示，PCK2在结直肠癌组织中的高表达与更好的无病生存相关，支持PCK2作为一个有希望的治疗靶点。这些发现表明，CM-NAG可能代表着与阿司匹林相比具有更高疗效和安全性的新一代抗肿瘤药物，为癌症治疗提供了新的前景。

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

Apoptosis 生物-生化与分子生物学

CiteScore

9.10

自引率

4.20%

发文量

审稿时长

1 months

期刊介绍： Apoptosis, a monthly international peer-reviewed journal, focuses on the rapid publication of innovative investigations into programmed cell death. The journal aims to stimulate research on the mechanisms and role of apoptosis in various human diseases, such as cancer, autoimmune disease, viral infection, AIDS, cardiovascular disease, neurodegenerative disorders, osteoporosis, and aging. The Editor-In-Chief acknowledges the importance of advancing clinical therapies for apoptosis-related diseases. Apoptosis considers Original Articles, Reviews, Short Communications, Letters to the Editor, and Book Reviews for publication.