2. Academic Validation
  3. Exploration of the antitumor effect and mechanism of gambogic acid on osteosarcoma through network pharmacology and experimental pharmacology study

Exploration of the antitumor effect and mechanism of gambogic acid on osteosarcoma through network pharmacology and experimental pharmacology study

  • Sci Rep. 2025 Jul 1;15(1):21647. doi: 10.1038/s41598-025-05308-2.
Mei Hu # 1 2,  Zhe Zhang # 1 2,  Cui Yan # 1,  Ximin Wang 1 2,  Jun Tong 1 2,  Guangru Li 3,  Xianjing Hu 4,  Congyan Zeng 5 6,  Weibo Dai 7 8,  Dawei Gao 9
Affiliations

Affiliations

  • 1 Zhongshan Hospital of Traditional Chinese Medicine, Guangzhou University of Traditional Chinese Medicine, Zhongshan, 528401, China.
  • 2 Hospital Prepration Transformation Branch, National Bngineering Research Center for Modernization of Traditional Chinese Medicine, Zhongshan, 528401, Guangdong, China.
  • 3 Zhanjiang Institute of Clinical Medicine, Central People's Hospital of Zhanjiang, Zhanjiang, 524000, Guangdong, China.
  • 4 Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, 523808, China.
  • 5 Zhongshan Hospital of Traditional Chinese Medicine, Guangzhou University of Traditional Chinese Medicine, Zhongshan, 528401, China. zszcy@126.com.
  • 6 Hospital Prepration Transformation Branch, National Bngineering Research Center for Modernization of Traditional Chinese Medicine, Zhongshan, 528401, Guangdong, China. zszcy@126.com.
  • 7 Zhongshan Hospital of Traditional Chinese Medicine, Guangzhou University of Traditional Chinese Medicine, Zhongshan, 528401, China. daiweibo007@163.com.
  • 8 Hospital Prepration Transformation Branch, National Bngineering Research Center for Modernization of Traditional Chinese Medicine, Zhongshan, 528401, Guangdong, China. daiweibo007@163.com.
  • 9 Zhongshan Hospital of Traditional Chinese Medicine, Guangzhou University of Traditional Chinese Medicine, Zhongshan, 528401, China. gaodawei0829@163.com.
  • # Contributed equally.
PMID: 40594358 DOI: 10.1038/s41598-025-05308-2
Abstract

Osteosarcoma (OS) is a highly aggressive bone Cancer in children and adolescents with extremely poor prognosis. Gambogic acid (GA) is a natural compound derived from the resin of Garcinia hanburyi trees and has been reported to possess multiple antitumor effects. However, the comprehensive mechanism of GA intervention in OS remains unclear. In this study, network pharmacology and experiment pharmacology were employed to elucidate the mechanism by which GA inhibited OS. Firstly, GA exhibited significant inhibitory effects on OS in vitro and in vivo. Then, the network pharmacological analysis and molecular docking predicted 9 targets involved in Necroptosis and Apoptosis induced by GA in OS. The qRT-PCR and western blotting verified that GA could increase the apoptosis-related mRNA and protein expression levels, such as cleaved Caspase-3, cleaved PARP, indicating that GA could activate Apoptosis. Furthermore, proteins related to Necroptosis such as RIPK1, RIPK3, and p-RIPK3 were upregulated, while MLKL initially increased and then decreased, implying a dynamic regulation of Necroptosis signaling. In summary, our results identified potential targets and pathways of GA to exert anti-osteosarcoma effect, suggesting that GA is a candidate drug for the treatment of osteosarcoma.

Keywords

Apoptotic; Experimental verification; Gambogic acid; Necroptosis; Network pharmacology; Osteosarcoma.

Figures
Products