Guggulsterone suppresses osteosarcoma progression by inhibiting glycolysis through MAPK signaling pathway

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-06-06 DOI:10.1016/j.phymed.2025.156949

Qijing Wang , Xuhui Yuan , Hongyan Li , Jiayu Li , Zhaoyang Wu , Wenming Zhang , Xinyu Fang

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引用次数: 0

Abstract

Background

Osteosarcoma (OS) represents an aggressive primary cancer originating in bone. It is predominantly diagnosed in pediatric and young adult populations, constituting approximately 20 % of bone malignancies in these age groups. Treatment efficacy is often hampered by chemoresistance. Guggulsterone (GS), a plant-derived sterol from Commiphora wightii, demonstrates promising anti-tumor potential, yet its effects on OS remain unexplored.

Purpose

The objective of this research was to clarify the anti-cancer mechanisms through which GS acts in OS and to evaluate its therapeutic prospects, with a particular focus on its influence over glycolysis and related signaling pathways.

Methods

In vitro investigations involved assessing cell viability, colony formation capability, apoptosis via flow cytometry, migration using Transwell assays, and protein levels by Western blot. Transcriptomic changes were evaluated using RNA sequencing. The anti-tumor efficacy of GS in vivo was confirmed using xenograft tumor models.

Results

GS treatment led to a significant decrease in OS cell proliferation, induced cell cycle arrest at the G2/M phase, and promoted apoptosis. Furthermore, GS suppressed OS cell migration and invasion, concurrent with modulation of proteins related to epithelial-mesenchymal transition (EMT). Mechanistically, GS targeted the MAPK signaling pathway, which resulted in impaired glycolytic activity and altered cellular energy metabolism. In vivo, administration of GS curtailed tumor growth without inducing noticeable systemic toxicity.

Conclusion

GS effectively counteracts OS progression by inhibiting glycolysis through MAPK pathway suppression. These findings suggest GS represents a promising therapeutic avenue for OS treatment.

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谷固酮通过抑制糖酵解MAPK信号通路抑制骨肉瘤进展

骨肉瘤（OS）是一种起源于骨的侵袭性原发癌症。它主要在儿科和年轻成人人群中被诊断出来，约占这些年龄组骨恶性肿瘤的20%。化疗耐药往往影响治疗效果。古古酮（Guggulsterone， GS）是一种从植物中提取的甾醇，具有良好的抗肿瘤潜力，但其对OS的影响尚不清楚。本研究的目的是阐明GS在OS中的抗癌机制，并评估其治疗前景，特别关注其对糖酵解和相关信号通路的影响。方法体外研究包括通过流式细胞术评估细胞活力、集落形成能力、细胞凋亡、Transwell迁移和Western blot检测蛋白水平。使用RNA测序评估转录组学变化。通过异种移植肿瘤模型证实了GS在体内的抗肿瘤作用。结果gs可显著抑制OS细胞增殖，诱导细胞周期阻滞于G2/M期，促进细胞凋亡。此外，GS抑制OS细胞的迁移和侵袭，同时调节上皮-间质转化（EMT）相关蛋白。在机制上，GS靶向MAPK信号通路，导致糖酵解活性受损和细胞能量代谢改变。在体内，给药GS抑制肿瘤生长而不引起明显的全身毒性。结论通过抑制MAPK通路抑制糖酵解，有效抑制OS进展。这些发现表明，GS代表了一种很有希望的治疗OS的途径。

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

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.