Details

Autor(en) / Beteiligte

• Tsai, Cheng-Fang
• Chen, Jia-Hong
• Chang, Chen-Ni
• Lu, Dah-Yuu
• Chang, Pei-Chun
• Wang, Shu-Lin
• Yeh, Wei-Lan

Titel

Fisetin inhibits cell migration via inducing HO-1 and reducing MMPs expression in breast cancer cell lines

Ist Teil von

• Food and chemical toxicology, 2018-10, Vol.120, p.528-535

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Metastasis is commonly seen in advanced stage of cancers, and matrix metalloproteinases (MMPs) are commonly up-regulated and have been identified as critical regulators. In this present study, a flavonoid, fisetin, which can be found in diverse foods, is investigated for its ability to inhibit cell motility, and the underlying mechanism is also studied in breast cancer cells (4T1 and JC cells). We have revealed that fisetin increased HO-1 mRNA and protein expressions. Besides, fisetin also elevated Nrf2 expression in nuclear fraction. By silencing Nrf2, fisetin-induced HO-1 expression was abrogated, suggested that HO-1 expression was mediated by up-regulation of the transcription factor Nrf2. In addition, we also found that fisetin decreased MMP-2 and MMP-9 enzyme activity and gene expression in both protein and mRNA levels. Moreover, by administration of HO-1 inhibitors, tin protoporphyrin and zinc protoporphyrin, fisetin-reduced MMP-2 and MMP-9 expressions were reversed. Furthermore, transfection of siRNA against HO-1 and Nrf2 also abolished MMP-2 and MMP-9 reduction exerted by fisetin. These findings suggest that fisetin-mediated MMP-2 and MMP-9 reduction is regulated by HO-1 through Nrf2. Therefore, fisetin may be useful as a potential therapeutic agent for the treatment of metastatic breast cancer. Fisetin, a flavonoid which can be found in diverse foods, has been found to increase Nrf2 expression in the nuclear fraction and enhance the transcription of heme oxidase (HO-1) of breast cancer cells, and consequently leads to decreased MMP-2 and MMP-9 expression and cell motility. Therefore, fisetin may be useful as a potential therapeutic agent for the treatment of metastatic breast cancer. [Display omitted] •Fisetin inhibits breast cancer motility.•Fisetin induces heme oxygenase-1 expression through Nrf2 regulation.•Fisetin-decreased MMP-2 and MMP-9 production is mediated by heme oxygenase-1.