Ziyuglycoside II suppressed the progression of osteosarcoma by coordinating estrogen-related receptor gamma and p53 signaling pathway.
10.1016/S1875-5364(25)60847-8
- Author:
Hang DU
1
;
Dongjin WU
1
;
Tianyu ZHANG
2
;
Ying ZHONG
1
;
Kaiyi WU
3
;
Xin GUO
3
;
Lisong SHENG
4
;
Nana HUANG
2
;
Chunzheng GAO
5
;
Rong SUN
6
Author Information
1. The Second Hospital of Shandong University, Jinan 250033, China.
2. The Second Hospital of Shandong University, Jinan 250033, China; Academy of Traditional Chinese Medicine, Shandong University of Traditional Chinese medicine Jinan 250355, China.
3. The Second Hospital of Shandong University, Jinan 250033, China; School of Pharmacy, Tianjin University of Traditional Chinese medicine, Tianjin 301617, China.
4. Advanced Medical Research Institute, Shandong University, Jinan 250012, China.
5. The Second Hospital of Shandong University, Jinan 250033, China. Electronic address: gaochunzheng1964@sina.com.
6. The Second Hospital of Shandong University, Jinan 250033, China; Advanced Medical Research Institute, Shandong University, Jinan 250012, China. Electronic address: sunrong@sdu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Cell cycle arrest;
Estrogen-related receptor gamma;
Osteosarcoma;
Ziyuglycoside II;
p53
- MeSH:
Osteosarcoma/physiopathology*;
Tumor Suppressor Protein p53/genetics*;
Humans;
Animals;
Saponins/chemistry*;
Bone Neoplasms/physiopathology*;
Signal Transduction/drug effects*;
Cell Line, Tumor;
Mice, Nude;
Mice;
Apoptosis/drug effects*;
Receptors, Estrogen/genetics*;
Mice, Inbred BALB C;
Female;
Male;
Xenograft Model Antitumor Assays
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(3):354-367
- CountryChina
- Language:English
-
Abstract:
Osteosarcoma (OS) is the most prevalent primary malignant bone tumor affecting children and adolescents. Despite ongoing research efforts, the 5-year survival rate has remained stagnant for many years, highlighting the critical need for novel drug development to enhance current treatment protocols. Ziyuglycoside II (ZYG II), a triterpenoid saponin extracted from S. officinalis, has recently demonstrated antitumor properties. This study evaluates the antitumor effect of ZYG II on osteosarcoma and elucidates its mechanism of action through the co-regulation of p53 and estrogen-related receptor gamma (ESRRG), which inhibits disease progression. The research employs in vitro experiments using multiple established osteosarcoma cell lines, as well as in vivo studies utilizing a nude mouse model of orthotopic xenograft osteosarcoma. Additionally, ESRRG shRNA was used to construct stable ESRRG-reducing OS cell lines to investigate the molecular mechanism by which ZYG II exerts its anti-osteosarcoma effects through the co-regulation of ESRRG and p53. Results indicate that ZYG II administration led to decreased OS cell viability and reduced tumor volumes. Furthermore, cell cycles were arrested at the G0/G1 phase, while the proportion of apoptotic cells increased. Expression of p53, ESRRG, p21, Bax, Cleaved Caspase-9, and Cleaved Caspase-3 proteins increased, while expression of CDK4, Cyclin D1, and Bcl-2 proteins decreased. Multiple ZYG II and ESRRG docking patterns were simulated through molecular docking. Comparing the pharmacodynamic response of ZYG II to OS cell lines with reduced ESRRG and normal expression demonstrated that ZYG II inhibits osteosarcoma progression, induces cell cycle arrest, and promotes cell apoptosis through the coordination of p53 and ESRRG. In conclusion, ZYG II inhibits osteosarcoma progression, leads to cell cycle arrest, and promotes cell apoptosis through synergistic regulation of p53 and ESRRG.
