期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 120, 期 -, 页码 528-535出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2018.07.059
关键词
Fisetin; Heme oxygenase-1; Matrix metalloproteinase; Migration; Breast cancer
资金
- Ministry of Science and Technology [MOST 106-2311-B-039-002, MOST 105-2320-B-468-004-MY3, 106-2813-C-039-115-B]
- China Medical University [CMU106-N-09, CMU106-SR-115, CMU106-ASIA-07]
- Taichung Tzu Chi Hospital [TTCRD107-03]
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, fisetininduced 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.
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