2. Academic Validation
  3. Marsdenia tenacissima extract accelerates ferroptosis of osteosarcoma cells by upregulating HO-1 and activating mitophagy

Marsdenia tenacissima extract accelerates ferroptosis of osteosarcoma cells by upregulating HO-1 and activating mitophagy

  • J Ethnopharmacol. 2025 Jun 26:350:120055. doi: 10.1016/j.jep.2025.120055.
Danfeng Xiang 1,  Xiangqi Zhang 2,  Xiaochuan Xue 3,  Hanlu Liang 4,  Jingjing Meng 5,  Shuai Zhao 6,  Jiao Yang 7,  Yangyun Zhou 8,  Yujie Hu 9,  Lingyan Xu 10,  Meizhi Shi 11,  Jingxian Zhang 12,  Mengyue Wang 13,  Junjun Chen 14,  Yonglong Han 15
Affiliations

Affiliations

  • 1 College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China; Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: danfenga243271024@163.com.
  • 2 Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: xiangqizhang@sjtu.edu.cn.
  • 3 College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China; Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: 2946794965@qq.com.
  • 4 College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China; Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: 1962014870@qq.com.
  • 5 Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: 17857699303@163.com.
  • 6 College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China; Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: 2382696952@qq.com.
  • 7 Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: yangjiaolily@126.com.
  • 8 Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: zhouyangyun945@163.com.
  • 9 Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: yujiehu0812@163.com.
  • 10 Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: cjgfwp@163.com.
  • 11 Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: emily0216@yeah.net.
  • 12 Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: jingxian0128@126.com.
  • 13 School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: mywang@sjtu.edu.cn.
  • 14 Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: chenjunjun8812@sjtu.edu.cn.
  • 15 College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China; Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: yonglongh@sjtu.edu.cn.
PMID: 40441459 DOI: 10.1016/j.jep.2025.120055
Abstract

Ethnopharmacological relevance: Marsdenia tenacissima extract (MTE) from the stem of the Traditional Chinese herbal medicine of Marsdenia tenacissima (Roxb.) Wight et Arn. has been used as an Anticancer remedy for decades.

Aim of the study: To investigate the beneficial effects of MTE in osteosarcoma in vitro and in vivo and its potential mechanisms.

Material and methods: Nude mice with ectopic xenograft tumors were treated with MTE of 10 mg/kg and 20 mg/kg for 2 weeks. Human osteosarcoma (OS) cell lines 143B and MG63 were treated with 40, 60, and 80 mg/mL MTE for 24 h.

Results: MTE significantly inhibited OS cell proliferation in vitro and in vivo. Specifically, intracellular ferrous ion accumulation is closely related to the upregulation of HO-1 expression levels regulated by MTE. NAC and DFO could restore the effects of MTE on OS cell viability. In addition, the Fe2+ accumulation caused cellular oxidative stress and promoted HO-1 translocation to mitochondria. Correspondingly, the mitochondria were damaged, lysosomes were recruited around, and the expression of autophagy-related proteins PINK1 and Parkin was upregulated. Moreover, the Autophagy inhibitor 3-MA reversed the effect of MTE on HO-1 and GPX4 protein expression levels in OS cells. In vivo experiments demonstrated that MTE inhibited the growth of xenograft osteosarcoma while increasing the expression of LC3B, HO-1 and FTH1, and simultaneously suppressing the level of GPX4 in tumor tissues.

Conclusion: MTE exerts anti-osteosarcoma effects by modulating HO-1 and activating Mitophagy, thereby accelerating the Ferroptosis.

Keywords

Ferroptosis; HO-1; Marsdenia tenacissima extract; Mitophagy; Osteosarcoma.

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