Juglone targets CBS to inhibit the Wnt/β-catenin pathway and promotes osteosarcoma cell apoptosis

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2026-06-19 Epub Date: 2026-04-24 DOI:10.1016/j.isci.2026.115867

Chengguang Wang , Shaoquan Liu , Hongli Xia , Shuqing Zhou , Jingjin Ma , Xinyu Yang , Junhong Chen , Shuaijun Hu , Ke Tang , Zhengxue Quan

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Abstract

Osteosarcoma (OS) is a severe primary bone cancer with current treatments facing high toxicity and limited success against metastasis. This study’s bioinformatics identified cystathionine beta-synthase (CBS) as a critical oncogene in OS, linked to poor prognosis via the Wnt/β-catenin pathway. CBS was manipulated in HOS and MG-63 cell lines to confirm its tumor-promoting role. Through the HERB database, juglone was discovered as a potential CBS inhibitor. Experiments showed juglone markedly inhibited OS cell proliferation, migration, invasion, and colony formation, while inducing cell death and G2/M phase arrest. Juglone degraded CBS and suppressed the Wnt/β-catenin pathway, reducing β-catenin and c-Myc levels. In vivo, juglone significantly reduced tumor growth in mice without toxicity. Clinical analysis confirmed CBS overexpression correlates with OS progression. These findings highlight juglone’s potential as a safe, effective anti-tumor agent targeting the CBS-Wnt/β-catenin pathway.

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核桃酮靶向CBS抑制Wnt/β-catenin通路，促进骨肉瘤细胞凋亡

骨肉瘤（Osteosarcoma， OS）是一种严重的原发性骨癌，目前的治疗面临着高毒性和有限的成功转移。本研究的生物信息学鉴定出胱硫氨酸β-合成酶（CBS）是OS的一个关键致癌基因，通过Wnt/β-catenin通路与预后不良相关。在HOS和MG-63细胞系中操纵CBS以证实其促肿瘤作用。通过HERB数据库，发现木酮是一种潜在的CBS抑制剂。实验表明，核桃酮可显著抑制OS细胞的增殖、迁移、侵袭和集落形成，同时诱导细胞死亡和G2/M期阻滞。核桃酮降解CBS，抑制Wnt/β-catenin通路，降低β-catenin和c-Myc水平。在体内实验中，核桃酮可显著抑制小鼠肿瘤生长，且无毒性。临床分析证实CBS过表达与OS进展相关。这些发现强调了核桃酮作为一种安全、有效的靶向CBS-Wnt/β-catenin通路的抗肿瘤药物的潜力。

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

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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