Fisetin regulates astrocyte migration and proliferation in vitro

Wang,Nan; Yao,Fang; Li,Ke; Zhang,Lanlan; Yin,Guo; Du,Mingjun; Wu,Bingyi

doi:10.3892/ijmm.2017.2890

Fisetin regulates astrocyte migration and proliferation in vitro

Authors:
- Nan Wang
- Fang Yao
- Ke Li
- Lanlan Zhang
- Guo Yin
- Mingjun Du
- Bingyi Wu
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Affiliations: Research Center of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Published online on: February 15, 2017 https://doi.org/10.3892/ijmm.2017.2890
Pages: 783-790
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Fisetin (3,3',4',7-tetrahydroxyflavone) is a plant flavonol found in fruits and vegetables that has been reported to inhibit migration and proliferation in several types of cancer. Reactive astrogliosis involves astrocyte migration and proliferation, and contributes to the formation of glial scars in central nervous system (CNS) disorders. However, the effect of fisetin on the migration and proliferation of astrocytes remains unclear. In this study, we found that fisetin inhibited astrocyte migration in a scratch-wound assay and diminished the phosphorylation of focal adhesion kinase (FAK; Tyr576/577 and paxillin (Tyr118). It also suppressed cell proliferation, as indicated by the decreased number of 5-ethynyl-2'-deoxyuridine (EdU)-positive cells, induced cell cycle arrest in the G1 phase, reduced the percentage of cells in the G2 and S phase (as measured by flow cytometry), and decreased cyclin D1 expression, but had no effect on apoptosis. Fisetin also decreased the phosphorylation levels of Akt and extracellular signal-regulated kinase (Erk)1/2, but had no effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK). These results indicate that fisetin inhibits aggressive cell phenotypes by suppressing cell migration and proliferation via the Akt/Erk signaling pathway. Fisetin may thus have potential for use as a therapeutic strategy targeting reactive astrocytes, which may lead to the inhibition of glial scar formation in vitro.

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