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Updated: Sep 19, 2025
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Guggulsterone suppresses osteosarcoma progression by inhibiting glycolysis through MAPK signaling pathway
Qijing Wang1, Xuhui Yuan2, Hongyan Li2
1Fujian Provincial Institute of Orthopedics, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Orthopaedic, Affiliated Mindong of Fujian Medical University, Fuan, China.
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.
Insights
Guggulsterone (GS) inhibits osteosarcoma (OS) progression by suppressing glycolysis via the MAPK pathway. This plant-derived compound shows therapeutic potential for treating OS, a common bone cancer in young people.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Osteosarcoma (OS) is an aggressive bone cancer primarily affecting pediatric and young adult populations.
- Chemoresistance often limits treatment efficacy in OS.
- Guggulsterone (GS), a plant sterol, shows anti-tumor potential but its role in OS is unknown.
Purpose of the Study:
- To elucidate the anti-cancer mechanisms of GS in OS.
- To evaluate GS's therapeutic potential, focusing on glycolysis and related signaling pathways.
Main Methods:
- In vitro: cell viability, colony formation, apoptosis, migration assays, Western blot, RNA sequencing.
- In vivo: xenograft tumor models to assess anti-tumor efficacy.
Main Results:
- GS reduced OS cell proliferation, induced G2/M cell cycle arrest, and promoted apoptosis.
- GS inhibited OS cell migration and invasion, affecting epithelial-mesenchymal transition (EMT) proteins.
- GS targeted the MAPK pathway, impairing glycolysis and altering cellular energy metabolism.
- In vivo studies showed GS curtailed tumor growth with no significant systemic toxicity.
Conclusions:
- GS effectively inhibits OS progression by suppressing glycolysis through MAPK pathway modulation.
- GS demonstrates promise as a therapeutic agent for osteosarcoma treatment.
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