Myricetin suppresses breast cancer metastasis through down‐regulating the activity of matrix metalloproteinase (MMP)‐2/9

Abstract

Tumour metastasis is the major cause of breast cancer mortality. Myricetin, a natural polyphenol, is found in teas, wines, and berries. The pharmacodynamic action and molecular mechanism of myricetin on breast cancer metastasis remain unknown. Here, we investigated the effect of myricetin on MDA-Mb-231Br cell viability, migration, invasion, and 4T1 mouse lung metastasis mouse models. MMP-2/9 protein expression and ST6GALNAC5 expression were analysed using western blot assays and quantitative real-time polymerase chain reaction, respectively. Cell migration and invasion were detected by wound-healing and Boyden transwell assays. The antimetastatic effect in vivo was evaluated by lung metastasis model. Myricetin significantly decreased the activities of MMP-2/9 and mRNA levels of ST6GALNAC5. In addition, the migration, invasion, and adhesion were effectively inhibited in a concentration-dependent manner. On the other hand, mice treated with myricetin exhibited smaller tumour nodules compared with the vehicle mice, with only 17.78 ± 15.41% after treatment with 50 mg/kg myricetin. In conclusion, myricetin could significantly block invasion of MDA-Mb-231Br cells through suppressing the protein expression of MMP-2/9 and the expression of ST6GALNAC5, as well as lung metastasis in a mouse model, which suggests that myricetin should be developed as a potential therapeutic candidate for breast cancer.

Flavonoids in Cancer Metastasis

“…Myricetin . Myricetin suppressed lung metastases in the 4T1 mouse model in vivo as well as migration, invasion, and metastasis in the MDA-Mb-231Br breast cancer cell line in vitro by suppression of MMP-2/-9 protein expression as well as expression of ST6GALNAC5, which is specifically expressed in brain metastatic cell lines and upregulated in brain metastasis patients [ 78 ]. Similarly, anti-metastatic properties of myricetin against cholangiocarcinoma KKU-100 cells were mediated partly through suppression of STAT3 pathway.…”

RUNX3 Inhibits the Invasion and Metastasis of Human Colon Cancer HT‐29 Cells by Upregulating MMP‐2/9

“…In addition, RUNX3 is involved in the regulation of epithelial-mesenchymal transition (EMT) by Evidence-Based Complementary and Alternative Medicine directly regulating the transcription of blocking protein-1, thus inhibiting tumor invasion and metastasis by protecting nesting apoptosis [22]. MMP-2 can break the degradation balance of matrix, induce cancer cells to penetrate the barrier formed by extracellular matrix and basement membrane, and reduce the adhesion between cells, so that cancer cells can infiltrate, invade, and metastasize to distant organs in surrounding tissues [23,24]. In the process of degradation, large amounts of vascular endothelial growth factors stored in the extracellular matrix can be released to induce tumor angiogenesis and provide the necessary nutritional basis and pathway for tumor cell invasion [25].…”

Bioactive Compounds: Natural Defense Against Cancer?

“…In a rat model, tumor progression was inhibited when the rats were fed with 100 mg/kg of myricetin, which was found to be due to inhibition of the p21 activated kinase-1 (PAK1) [100]. A recent study showed that myricetin may exert anti-metastatic effects by downregulating the expression of MMP2 and/or MMP9 in breast cancer cells [101]. Myricetin is stable at pH 2 and its degradation depends on pH and temperature [91].…”