2. Academic Validation
  3. Artesunate activates the ATF4-CHOP-CHAC1 pathway and affects ferroptosis in Burkitt's Lymphoma

Artesunate activates the ATF4-CHOP-CHAC1 pathway and affects ferroptosis in Burkitt's Lymphoma

  • Biochem Biophys Res Commun. 2019 Nov 12;519(3):533-539. doi: 10.1016/j.bbrc.2019.09.023.
Ning Wang 1,  Guang-Zhi Zeng 1,  Jun-Lin Yin 2,  Zhao-Xiang Bian 3
Affiliations

Affiliations

  • 1 Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission and Ministry of Education, Yunnan Minzu University, Kunming, Yunnan, China.
  • 2 Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission and Ministry of Education, Yunnan Minzu University, Kunming, Yunnan, China. Electronic address: [email protected].
  • 3 Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. Electronic address: [email protected].
PMID: 31537387 DOI: 10.1016/j.bbrc.2019.09.023
Abstract

Currently, there is no effective treatment for Burkitt's lymphoma in patients aged above 60 years, and thus research on effective treatment options for Burkitt's lymphoma has been gaining increasing attention. Artesunate has been identified as a novel effective growth suppressor in Burkitt's lymphoma. Here, we utilized Molecular Biology, transcriptome analysis, and other techniques to study artesunate-induced death of the Burkitt's lymphoma cells DAUDI and CA-46, the effect of artesunate on gene expression in DAUDI and CA-46 cells, and the effect of artesunate-induced ATF4-CHOP-CHAC1 pathway on Ferroptosis. We also studied the inhibitory effects and Ferroptosis induction of artesunate on CA-46 cells in mouse xenografts. Results showed that artesunate induced Ferroptosis in DAUDI and CA-46 cells, as evidenced by the protective effect of liproxstatin-1, ferrostatin-1, and desferoxamine, resulting in an endoplasmic reticulum stress response, activation of the ATF4-CHOP-CHAC1 pathway enhanced Ferroptosis in DAUDI and CA-46 cells. A mouse-transplanted tumor model showed that artesunate can inhibit the proliferation and induce Ferroptosis of CA-46 cells in vivo. This study provides a novel perspective for the development of drugs against different types of Burkitt's lymphomas.

Keywords

Artesunate; Burkitt's lymphoma; CHAC1; Ferroptosis; Xenograft.

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