Emodin inhibits U87 glioblastoma cells migration by activating aryl hydrocarbon receptor (AhR) signaling pathway

Li Xu; Yiyun Liu; Yangsheng Chen; Ruihong Zhu; Siqi Li; Songyan Zhang; Jian Zhang; Heidi Qunhui Xie; Bin Zhao

doi:10.1016/j.ecoenv.2022.113357

Emodin inhibits U87 glioblastoma cells migration by activating aryl hydrocarbon receptor (AhR) signaling pathway

Ecotoxicol Environ Saf. 2022 Apr 1:234:113357. doi: 10.1016/j.ecoenv.2022.113357. Epub 2022 Mar 7.

Authors

Li Xu¹, Yiyun Liu², Yangsheng Chen¹, Ruihong Zhu¹, Siqi Li¹, Songyan Zhang³, Jian Zhang³, Heidi Qunhui Xie⁴, Bin Zhao¹

Affiliations

¹ State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China; Institute of Environment and Health, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.
² State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China; School of Public Health and Management, Chongqing Medical University, Chongqing, China.
³ Engineering Laboratory of Shenzhen Natural Small Molecule Innovative Drugs, Health Science Center, Shenzhen University, Shenzhen, China.
⁴ State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China; Institute of Environment and Health, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China. Electronic address: qhxie@rcees.ac.cn.

PMID: 35272197
DOI: 10.1016/j.ecoenv.2022.113357

Abstract

Aryl hydrocarbon receptor (AhR) is a ligand-activated receptor to mediates the biological reactions of many environmental and natural compounds, which is highly expressed in glioblastoma. Although it has been reported that AhR agonist emodin can suppress some kinds of tumors, its inhibitory effect on glioblastoma migration and its relationship with AhR remain unclear. Based on the complexity of tumor pathogenesis and the tissue specificity of AhR, we hope can further understand the effect of emodin on glioblastoma and explore its mechanism. We found that the inhibitory effect of emodin on the migration of U87 glioblastoma cells increased with time, and the cell migration ability was inhibited by about 25% after 36 h exposure. In this process, emodin promoted the expression of the tumor suppressor IL24 by activating the AhR signaling pathway. Reducing the expression of AhR or IL24 by interfering RNA could block or relieve the inhibitory effect of emodin on the U87 cells migration, which indicates the inhibition of emodin on the migration of glioblastoma is mediated by the AhR-IL24 axis. Our data proved the AhR-IL24 signal axis is an important pathway for emodin to inhibit the migration of glioblastoma, and the AhR signaling pathway can be used as a key target to research the regulation effect and its mechanism of compounds on glioblastoma migration.

Keywords: Aryl hydrocarbon receptor; Emodin; Glioblastoma; Interleukin 24; Migration.