Fisetin inhibits liver cancer growth in a mouse model: Relation to dopamine receptor

Liu,Xiang-Feng; Long,Hai-Jiao; Miao,Xiong-Ying; Liu,Guo-Li; Yao,Hong-Liang

doi:10.3892/or.2017.5676

Fisetin inhibits liver cancer growth in a mouse model: Relation to dopamine receptor

Authors:
- Xiang-Feng Liu
- Hai-Jiao Long
- Xiong-Ying Miao
- Guo-Li Liu
- Hong-Liang Yao
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Affiliations: Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 421000, P.R. China
Published online on: May 30, 2017 https://doi.org/10.3892/or.2017.5676
Pages: 53-62
Copyright: © Liu 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), a natural abundant flavonoid, is produced in different vegetables and fruits. Fisetin has been reported to relate to various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. Dopamine receptors (DRs) belonging to G protein‑coupled receptor family, are known as the target of ~50% of all modern medicinal drugs. DRs consist of various proteins, functioning as transduction of intracellular signals for extracellular stimuli. We found that fisetin performed as DR2 agonist to suppress liver cancer cells proliferation, migration and invasion. Caspase-3 signaling was activated to induce apoptosis for fisetin administration. Furthermore, TGF‑β1 was also inhibited in fisetin-treated liver cancer cells, reducing epithelial-mesenchymal transition (EMT). Additionally, fisetin downregulated VEGFR1, p-ERK1/2, p38 and pJNK, ameliorating liver cancer progression. In vivo, the orthotopically implanted tumors from mice were inhibited by fisetin adminisatration accompanied by prolonged survival rate and higher levels of dopamine. Together, the results indicated a novel therapeutic strategy to suppress liver cancer progression associated with DR2 regulation, indicating that dopamine might be of importance in liver cancer progression.

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