2. Academic Validation
  3. Emodin induced necroptosis in the glioma cell line U251 via the TNF-α/RIP1/RIP3 pathway

Emodin induced necroptosis in the glioma cell line U251 via the TNF-α/RIP1/RIP3 pathway

  • Invest New Drugs. 2020 Feb;38(1):50-59. doi: 10.1007/s10637-019-00764-w.
Jiabin Zhou 1 2,  Genhua Li 2,  Guangkui Han 2,  Song Feng 2,  Yuhan Liu 3,  Jun Chen 2 4,  Chen Liu 2 4,  Lei Zhao 5,  Feng Jin 6
Affiliations

Affiliations

  • 1 Graduate School, Tianjin Medical University, Tianjin, 300070, People's Republic of China.
  • 2 Department of Neurosurgery, Affiliated Hospital of Jining Medical University, & Shandong Provincial Key Laboratory of Stem Cells and Neuro-oncology, Jining, Shandong, 272029, People's Republic of China.
  • 3 Department of Traditional Chinese Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
  • 4 Clinical Medical College, Jining Medical University, Jining, Shandong, 272029, People's Republic of China.
  • 5 Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 6 Department of Neurosurgery, Affiliated Hospital of Jining Medical University, & Shandong Provincial Key Laboratory of Stem Cells and Neuro-oncology, Jining, Shandong, 272029, People's Republic of China. jinfengsdjn@163.com.
PMID: 30924024 DOI: 10.1007/s10637-019-00764-w
Abstract

Emodin, an anthraquinone compound extracted from rhubarb and other traditional Chinese medicines, has been proven to have a wide range of pharmacological effects, such as anti-inflammatory, Antiviral, and antitumor activities. Previous studies have confirmed that emodin has inhibitory effects on various solid tumors, such as osteosarcoma, liver Cancer, prostate Cancer and glioma. This study aimed to investigate the effects and mechanisms of emodin-induced Necroptosis in the glioma cell line U251 by targeting the TNF-α/RIP1/RIP3 signaling pathway. We found that emodin could significantly inhibit U251 cell proliferation, and the viability of U251 cells treated with emodin was reduced in a dose- and time-dependent manner. Flow cytometry assays and Hoechst-PI staining assays showed that emodin induced Apoptosis and Necroptosis. Real-Time PCR and western blot analysis showed that emodin upregulated the levels of TNF-α, RIP1, RIP3 and MLKL. Furthermore, the RIP1 inhibitor Nec-1 and the RIP3 inhibitor GSK872 attenuated the killing effect of emodin on U251 cells. In addition, emodin could increase the levels of TNF-α, RIP1, RIP3 and MLKL in vivo. The results demonstrate that emodin could induce Necroptosis in glioma possibly through the activation of the TNF-α/RIP1/RIP3 axis. These studies provide novel insight into the induction of Necroptosis by emodin and indicate that emodin might be a potential candidate for treating glioma through the Necroptosis pathway.

Keywords

Emodin; Necroptosis; RIP1; RIP3; TNF-α; U251.

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