2. Academic Validation
  3. Triptonide stabilizes BIM to enhance oxaliplatin-induced ferroptosis and apoptosis in colorectal cancer

Triptonide stabilizes BIM to enhance oxaliplatin-induced ferroptosis and apoptosis in colorectal cancer

  • Transl Oncol. 2025 Oct:60:102491. doi: 10.1016/j.tranon.2025.102491.
Ji Ma 1,  Liyun Zheng 2,  Shiji Fang 2,  Wenjing Yang 2,  Yiming Ding 2,  Mengyuan Wang 2,  Jiale Chen 2,  Qiaoyou Weng 2,  Zouying Yao 3,  Chuan Jiang 4,  Minjiang Chen 2,  Hongtao Xu 5,  Jiansong Ji 6
Affiliations

Affiliations

  • 1 Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China; Department of radiology, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China; Department of Gastrointestinal surgery, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China.
  • 2 Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China; Department of radiology, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China.
  • 3 Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China.
  • 4 Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China; Department of Gastrointestinal surgery, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China.
  • 5 Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China; Department of Gastrointestinal surgery, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China. Electronic address: xht0071@sina.com.
  • 6 Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China; Department of radiology, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China. Electronic address: jjstcty@wmu.edu.cn.
PMID: 40773827 DOI: 10.1016/j.tranon.2025.102491
Abstract

Oxaliplatin (OXA) is a common chemotherapeutic agent for advanced colorectal Cancer. However, its effectiveness is limited by drug resistance, highlighting the need for combination therapies. In this study, Triptonide (TN), a diterpenoid compound is used to enhance the sensitivity of OXA, and the underlying mechanisms are investigated. Our findings indicated the combination of TN and OXA demonstrated strong synergistic anti-tumor effects across a broad concentration range in both HCT116 and LoVo cell lines, particularly at ratios ranging from 1:312 to 1:156. The combination of TN and OXA at low doses effectively inhibits growth and induces cell death in HCT116 and LoVo cells. TN and OXA cotreatment causes severe mitochondrial damage in colorectal Cancer cells, leading to intracellular Reactive Oxygen Species (ROS) accumulation, which subsequently triggers Apoptosis and Ferroptosis. Mechanistically, TN directly binds to Bim, a pro-apoptotic and ferroptotic protein, and stabilizes it. TN treatment led to increased expression of Bim and knockdown of Bim alleviated the growth inhibition of OXA in colorectal Cancer cells. Finally, TN and OXA cotreatment significantly reduced the tumor weight and volume of LoVo-bearing nude mice in vivo. Taken together, our findings indicate that TN may serve as a novel therapeutic agent to enhance the efficacy OXA in the treatment of colorectal Cancer.

Keywords

BIM; Colorectal cancer; Mitochondrial damage; Oxaliplatin; Oxidative stress; Triptonide.

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