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Updated: Jun 29, 2025

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Asiatic acid inhibits osteosarcoma cell migration and invasion via the AKT/Sp1/MMP1 axis
Yat-Yin Law1,2,3, Hsiang-Lin Lee1,4, Chu-Liang Lin3
1School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Abstract:
Osteosarcoma is a malignant bone tumor affecting adolescents and children. No effective treatment is currently available. Asiatic acid (AA), a triterpenoid compound found in Centella asiatica, possesses anti-tumor, anti-inflammatory, and anti-oxidant properties in various types of tumor cells. This study aims to determine whether AA exerts antitumor effects in human osteosarcoma cells. Our results indicate that AA does not influence the viability, proliferative rate, or cell cycle phase of human osteosarcoma cells under non-toxic conditions. AA suppressed osteosarcoma cell migration and invasion by down-regulating matrix metalloproteinase 1 (MMP1) expression. Data in the TNMplot database suggested MMP1 expression was higher in osteosarcoma than in normal tissues, with associated clinical significance observed in osteosarcoma patients. Overexpression of MMP1 in osteosarcoma cells reversed the AA-induced suppression of cell migration and invasion. AA treatment decreased the expression of specificity protein 1 (Sp1), while Sp1 overexpression abolished the effect of AA on MMP1 expression and cell migration and invasion. AA inhibited AKT phosphorylation, and treatment with a PI3K inhibitor (wortmannin) increased the anti-invasive effect of AA on osteosarcoma cells via the p-AKT/Sp1/MMP1 axis. Thus, AA exhibits the potential for use as an anticancer drug against human osteosarcoma.
Insights
Asiatic acid (AA) shows potential against osteosarcoma by inhibiting cancer cell migration and invasion. It targets the p-AKT/Sp1/MMP1 pathway, offering a new avenue for treating this bone cancer.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Osteosarcoma is a prevalent bone cancer in children and adolescents with limited treatment options.
- Asiatic acid (AA), derived from Centella asiatica, exhibits known anti-tumor properties in various cancer cell types.
- Investigating novel therapeutic agents for osteosarcoma is crucial due to the lack of effective treatments.
Purpose of the Study:
- To evaluate the antitumor effects of Asiatic acid (AA) on human osteosarcoma cells.
- To elucidate the molecular mechanisms underlying AA's action in osteosarcoma.
- To explore the potential of AA as a therapeutic agent for osteosarcoma.
Main Methods:
- Cell viability, proliferation, and cell cycle assays were performed.
- Cell migration and invasion assays were conducted.
- Gene expression analysis (MMP1, Sp1) and Western blotting (p-AKT) were utilized.
- Bioinformatic analysis of the TNMplot database was performed.
Main Results:
- Asiatic acid (AA) did not affect osteosarcoma cell viability, proliferation, or cell cycle.
- AA significantly suppressed osteosarcoma cell migration and invasion by down-regulating MMP1 expression.
- AA reduced Sp1 expression and AKT phosphorylation, key components of the p-AKT/Sp1/MMP1 pathway.
- MMP1 overexpression reversed AA's anti-migratory and anti-invasive effects, while Sp1 overexpression abolished AA's efficacy.
Conclusions:
- Asiatic acid (AA) demonstrates anti-invasive and anti-migratory effects on human osteosarcoma cells.
- The anti-cancer activity of AA is mediated through the p-AKT/Sp1/MMP1 signaling pathway.
- AA holds promise as a potential therapeutic candidate for osteosarcoma treatment.
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