2. Academic Validation
  3. Erianin, a novel dibenzyl compound in Dendrobium extract, inhibits lung cancer cell growth and migration via calcium/calmodulin-dependent ferroptosis

Erianin, a novel dibenzyl compound in Dendrobium extract, inhibits lung cancer cell growth and migration via calcium/calmodulin-dependent ferroptosis

  • Signal Transduct Target Ther. 2020 May 8;5(1):51. doi: 10.1038/s41392-020-0149-3.
Peng Chen  # 1 2 3 4,  Qibiao Wu  # 4,  Jiao Feng 1 3,  Lili Yan 1 3,  Yitian Sun 1 3,  Shuiping Liu 1 3,  Yu Xiang 1 3 5,  Mingming Zhang 1 3,  Ting Pan 1 3,  Xiaying Chen 1 3,  Ting Duan 1 3,  Lijuan Zhai 1 3 5,  Bingtao Zhai 1 3,  Wengang Wang 1 3,  Ruonan Zhang 1 3 4,  Bi Chen 1 3 4,  Xuemeng Han 1 3,  Yicong Li 6,  Liuxi Chen 1,  Ying Liu 7,  Xingxing Huang 1,  Ting Jin 1 3,  Wenzheng Zhang 1,  Hong Luo 1,  Xiaohui Chen 1,  Yongqiang Li 1,  Qiujie Li 1 3,  Guohua Li 1 3,  Qin Zhang 1 3,  Lvjia Zhuo 1 3,  Zuyi Yang 8,  Huifen Tang 8,  Tian Xie 9 10,  Xiaoping Ouyang 11,  Xinbing Sui 12 13 14
Affiliations

Affiliations

  • 1 Holistic Integrative Pharmacy Institutes and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
  • 2 Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 3 Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, China.
  • 4 State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, P.R. China.
  • 5 Zhejiang Chinese Medicinal University, Hangzhou, China.
  • 6 Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
  • 7 Department of Medical Oncology, Zhejiang University, Hangzhou, China.
  • 8 Department of Hematology and Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
  • 9 Holistic Integrative Pharmacy Institutes and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China. xbs@hznu.edu.cn.
  • 10 Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, China. xbs@hznu.edu.cn.
  • 11 Radiation Detection Research Center, Northwest Institute of Nuclear Technology, Xi'an, China. droyxp@aliyun.com.
  • 12 Holistic Integrative Pharmacy Institutes and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China. hzzju@zju.edu.cn.
  • 13 Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, China. hzzju@zju.edu.cn.
  • 14 Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China. hzzju@zju.edu.cn.
  • # Contributed equally.
PMID: 32382060 DOI: 10.1038/s41392-020-0149-3
Abstract

Ferroptosis, a novel form of programmed cell death, is characterized by iron-dependent lipid peroxidation and has been shown to be involved in multiple diseases, including Cancer. Stimulating Ferroptosis in Cancer cells may be a potential strategy for Cancer therapy. Therefore, ferroptosis-inducing drugs are attracting more attention for Cancer treatment. Here, we showed that erianin, a natural product isolated from Dendrobium chrysotoxum Lindl, exerted its Anticancer activity by inducing cell death and inhibiting cell migration in lung Cancer cells. Subsequently, we demonstrated for the first time that erianin induced ferroptotic cell death in lung Cancer cells, which was accompanied by ROS accumulation, lipid peroxidation, and GSH depletion. The Ferroptosis inhibitors Fer-1 and Lip-1 but not Z-VAD-FMK, CQ, or necrostatin-1 rescued erianin-induced cell death, indicating that Ferroptosis contributed to erianin-induced cell death. Furthermore, we demonstrated that CA2+/CaM signaling was a critical mediator of erianin-induced Ferroptosis and that blockade of this signaling significantly rescued cell death induced by erianin treatment by suppressing Ferroptosis. Taken together, our data suggest that the natural product erianin exerts its Anticancer effects by inducing CA2+/CaM-dependent Ferroptosis and inhibiting cell migration, and erianin will hopefully serve as a prospective compound for lung Cancer treatment.

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