2. Academic Validation
  3. Erianin triggers ferroptosis in colorectal cancer cells by facilitating the ubiquitination and degradation of GPX4

Erianin triggers ferroptosis in colorectal cancer cells by facilitating the ubiquitination and degradation of GPX4

  • Phytomedicine. 2025 Apr:139:156465. doi: 10.1016/j.phymed.2025.156465.
Yuting Zheng 1,  Yinli Zheng 2,  Haipeng Chen 3,  Xuanjing Tan 4,  Guiyu Zhang 5,  Muyan Kong 6,  Ruidi Jiang 7,  Hong Yu 8,  Keyao Shan 9,  Jiyao Liu 10,  Rong Zhang 11,  Zhongqiu Liu 12,  Jinjun Wu 13
Affiliations

Affiliations

  • 1 State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China. Electronic address: 13642455322@163.com.
  • 2 State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Department of Pathology, Guangzhou 510060, China. Electronic address: zhengyinl@sysucc.org.cn.
  • 3 State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China. Electronic address: C1251343392@163.com.
  • 4 State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China. Electronic address: txjrabbit@163.com.
  • 5 State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China; The Seventh Affiliated Hospital of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518000, China. Electronic address: zhangguiyu@gzucm.edu.cn.
  • 6 The Seventh Affiliated Hospital of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518000, China. Electronic address: kmy_1995n@163.com.
  • 7 State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China. Electronic address: ruidi2001@126.com.
  • 8 State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China. Electronic address: 15310505297@163.com.
  • 9 State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China. Electronic address: sky1020189@163.com.
  • 10 State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China. Electronic address: liu_jiyao@163.com.
  • 11 State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China. Electronic address: zhangrong@gzucm.edu.cn.
  • 12 State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China. Electronic address: liuzq@gzucm.edu.cn.
  • 13 State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China. Electronic address: wujinjun@gzucm.edu.cn.
PMID: 39938177 DOI: 10.1016/j.phymed.2025.156465
Abstract

Background: Colorectal Cancer (CRC) continues to represent a significant global public health challenge. Ferroptosis, a novel form of cell death dependent on iron and involving lipid peroxidation, has emerged as an effective strategy for treating various cancers with great potential for application.

Purpose: This study aimed to investigate the therapeutic potential of erianin, a novel dibenzyl compound isolated from the well-known herbal medicine Dendrobium chrysotoxum Lindl, in the treatment of CRC through induction of Ferroptosis.

Methods: Human CRC HCT116 and SW480 cells were employed for in vitro investigations, while an AOM/DSS CRC animal model was established for in vivo experiments.

Results: The results demonstrated that erianin effectively inhibited the growth of CRC cells and suppressed tumorigenesis in the AOM/DSS CRC animal model. Erianin induced Ferroptosis in CRC cells as evidenced by a significant increase in intracellular Fe2+ levels and lipid peroxides, along with a decrease in glutathione. Additionally, Ferroptosis inhibitors reversed the cytotoxicity of erianin against CRC cells as well as its induction of Ferroptosis. Notably, novel Glutathione Peroxidase 4 (GPX4), a core regulatory factor of Ferroptosis, was found to be overexpressed in human primary colon adenocarcinoma tissues compared with normal tissues. However, erianin significantly reduced GPX4 expression by facilitating its ubiquitination and degradation. Furthermore, the overexpression of GPX4 mitigated erianin-induced ferroptotic cell death; conversely, the silencing of GPX4 amplified these effects.

Conclusion: Erianin demonstrates the potential to inhibit CRC by inducing Ferroptosis through accelerating the ubiquitination and degradation of GPX4, indicating its promise as a therapeutic candidate against CRC.

Keywords

Colorectal cancer; Erianin; Ferroptosis; GPX4; Ubiquitination.

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