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AHR activation in glioblastoma cells [I3CA_U87]

ABSTRACT: The objective of this study was to analyze AHR activation through aromatic amino acid metabolism. To this end, glioblastoma cells were exposed to aromatic amino acid derived metabolites and their ability to activate AHR was analysed. In addition, AHR activation was evaluated in glioblastoma cells expressing IL4I1, an aromatic amino acid degrading enzyme, with or without shRNA mediated knockdown of AHR.

ORGANISM(S): Homo sapiens

PROVIDER: GSE129974 | GEO | 2020/08/19

REPOSITORIES: GEO

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AHR activation in glioblastoma cells [IL4I1_shAHR_U87]

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Project description:Glioblastoma is the most frequent and aggressive primary astrocytoma in adults. The high migration ability of the tumor cells is an important reason for the high recurrence rate and poor prognosis of glioblastoma. Recently, emerging evidence has shown that the migration ability of glioblastoma cell was inhibited upon the activation of aryl hydrocarbon receptor (AhR), suggesting potential anti-tumor effects of AhR agonists. Rutaecarpine is a natural compound with potential tumor therapeutic effects which can possibly bind to AhR. However, its effect on the migration of glioblastoma is unclear. Therefore, we aim to explore the effects of rutaecarpine on the migration of human glioblastoma cells U87 and the involvements of the AhR signaling pathway. The results showed that: (i) compared with other structural related alkaloids, like evodiamine and dehydroevodiamine, rutaecarpine was a more potent AhR activator, and has stronger inhibitory effect on the glioblastoma cell migration; (ii) rutaecarpine decreased the migration ability of U87 cells in an AhR-dependent manner; (iii) AhR mediated the expression of a tumor suppressor interleukin 24 (IL24) induced by rutaecarpine, and AhR-IL24 axis was involved in the anti-migratoryeffects of rutaecarpine on the glioblastoma. Besides IL24, other motility related genes were proposed to participate in the migration regulation process of rutaecarpine by RNA-Seq analysis. These data suggest that rutaecarpine is a natural AhR agonist that could inhibit the migration of glioblastomaandbe a potential candidate for developing therapeutic drug against glioblatoma.

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