2. Academic Validation
  3. Pulsatilla saponin D inhibited the growth of osteosarcoma by regulating the JNK/ATF3 signaling pathway

Pulsatilla saponin D inhibited the growth of osteosarcoma by regulating the JNK/ATF3 signaling pathway

  • Chem Biol Interact. 2025 Feb 13:410:111420. doi: 10.1016/j.cbi.2025.111420.
Kaipeng Jin 1,  Chengchun Shen 1,  Wei Yu 1,  Jinti Lin 1,  Jian Zhu 1,  Huimin Tao 2,  Bing Liu 3
Affiliations

Affiliations

  • 1 Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China; Clinical Research Center of Motor System Disease of Zhejiang Province, PR China; Zhejiang Key Laboratory of Motor System Disease Precision Research and Therapy, Hangzhou City, Zhejiang Province, PR China; State Key Laboratory of Transvascular Implantation Devices, Hangzhou, 310009, PR China.
  • 2 Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China; Clinical Research Center of Motor System Disease of Zhejiang Province, PR China; Zhejiang Key Laboratory of Motor System Disease Precision Research and Therapy, Hangzhou City, Zhejiang Province, PR China; State Key Laboratory of Transvascular Implantation Devices, Hangzhou, 310009, PR China. Electronic address: 2187040@zju.edu.cn.
  • 3 Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China; Clinical Research Center of Motor System Disease of Zhejiang Province, PR China; Zhejiang Key Laboratory of Motor System Disease Precision Research and Therapy, Hangzhou City, Zhejiang Province, PR China; State Key Laboratory of Transvascular Implantation Devices, Hangzhou, 310009, PR China. Electronic address: liubingzju@zju.edu.cn.
PMID: 39954838 DOI: 10.1016/j.cbi.2025.111420
Abstract

Osteosarcoma (OS) is a highly malignant and aggressive bone tumor associated with early lung metastasis and high mortality. Traditional chemotherapy does not effectively improve the efficacy and survival rate of patients with OS. Thus, it is vital to search for alternative therapies. Pulsatilla saponin D (PSD) is a potent bioactive compound that has been widely employed in Cancer therapy due to its diverse bioactivities and minimal adverse effects. However, any effect on OS remains unclear. We found that PSD induced Apoptosis of OS cells and investigated the mechanisms thereof. In vitro, PSD dose-dependently induced Apoptosis and inhibited the viability of HOS and K7M2 cells. Furthermore, PSD significantly suppressed cell migration and invasion, and caused cell cycle arrest at the G0/G1 phase. Mechanistically, PSD upregulated ATF3 and JUN transcription by controlling JNK expression. Compared to cells treated with PSD alone, cells pre-treated with SP600125 (a JNK Inhibitor), or in which ATF3 had been knocked down ATF3 with siRNA, did not exhibit PSD-mediated cell Apoptosis. In a murine OS model, PSD exhibited a powerful anti-cancer effect and an excellent safety profile. Our data imply that PSD could effectively prevent OS occurrence and progression.

Keywords

Apoptosis; Cell cycle; JNK/ATF3 signaling pathway; Osteosarcoma; Pulsatilla saponin D.

Figures
Products