Resveratrol inhibits the proliferation of estrogen receptor-positive breast cancer cells by suppressing EZH2 through the modulation of ERK1/2 signaling

  • Chunyan Hu
  • Yun Liu
  • Mengying Teng
  • Kailin Jiao
  • Jing Zhen
  • Maoxuan Wu
  • Zhong LiEmail author
Original Article


Enhancer of zeste homolog 2 (EZH2) is frequently overexpressed in breast cancer and plays an important role in maintaining the cell proliferative capacity. However, the mechanisms underlying the transcriptional regulation of EZH2 in estrogen receptor (ER)-positive breast cancer cells remain unclear. The antitumor effects of resveratrol have been reported. However, whether EZH2 was involved in these effects needs further exploration. Here, we showed that EZH2 is required for estrogen-induced cell proliferation in ER-positive breast cancer. Exposure to 17β-estradiol (E2) upregulated EZH2 via ERα signaling, and this effect was blocked by U0126, a MEK inhibiter. Resveratrol inhibited the proliferation and colony formation in ER-positive breast cancer cells and downregulated EZH2 through inhibition of phospho-ERK1/2. These findings indicated that ERK1/2 and ER signaling–mediated EZH2 upregulation is crucial for the proliferation of ER-positive breast cancer cells. The suppression of EZH2 expression by ERK1/2 dephosphorylation is important for the antiproliferative activities of resveratrol against ER-positive breast cancer cells.


EZH2 Estrogen receptor Phospho-ERK1/2 Resveratrol Proliferation 


Funding information

This work was supported by the National Natural Science Foundation of China [grant numbers 81573183, 81673205]; the Major Program of Natural Science Research of Jiangsu Higher Education Institutions [grant number 15KJA330001]; the Center for Global Health, School of Public Health, Nanjing Medical University; and the project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10565_2019_9471_MOESM1_ESM.doc (2.5 mb)
ESM 1 (DOC 2607 kb)


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Chunyan Hu
    • 1
  • Yun Liu
    • 1
  • Mengying Teng
    • 1
  • Kailin Jiao
    • 1
  • Jing Zhen
    • 1
  • Maoxuan Wu
    • 1
  • Zhong Li
    • 1
    Email author
  1. 1.Department of Nutrition and Food Hygiene, School of Public HealthNanjing Medical UniversityNanjingChina

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