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

Phytother Res. 2018 Jul;32(7):1373-1381. doi: 10.1002/ptr.6071. Epub 2018 Mar 13.

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.

Keywords: MMP-2/9; Myricetin; ST6GALNAC5; breast cancer; metastasis.

MeSH terms

  • Animals
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Down-Regulation
  • Female
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use*
  • Humans
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Metastasis

Substances

  • Flavonoids
  • myricetin
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9