Anticancer effect of metformin on estrogen receptor-positive and tamoxifen-resistant breast cancer cell lines

Jinkyoung Kim, Jiyun Lee, Soon Young Jang, Chungyeul Kim, Yoojin Choi, Aeree Kim

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


Acquisition of tamoxifen resistance (TR) during anti-estrogenic therapy using tamoxifen is a major obstacle in the treatment of estrogen receptor (ER)-positive breast cancer. As a biguanide derivative, metformin is commonly used to treat type II diabetes. It has recently emerged as a potential anticancer agent. The objective of the present study was to investigate the anticancer activity of metformin in relation to ERα expression and its signaling pathway in ERα-positive MCF-7 and MDA-MB-361 breast cancer cells as well as TR MCF-7 breast cancer cells. Metformin inhibited both protein and mRNA levels of ERα in the presence or absence of estrogen (E2) in the MCF-7, TR MCF-7 and MDA-MB-361 cells. Metformin repressed E2-inducible estrogen response element (ERE) luciferase activity, protein levels and mRNA levels of E2/ERα-regulated genes [including c-Myc, cyclin D1, progesterone receptor (PR) and pS2] to a greater degree than tamoxifen, resulting in inhibition of cell proliferation of MCF-7, TR MCF-7 and MDA-MB-361 cells. Collectively, our results suggest that one of the anticancer mechanisms of metformin could be attributable to the repression of expression and transcriptional activity of ERα. Metformin may be a good therapeutic agent for treating ERα-positive breast cancer by inhibiting the expression and function of ERα. In addition, metformin may be useful to treat tamoxifen-resistant breast cancer.

Original languageEnglish
Pages (from-to)2553-2560
Number of pages8
JournalOncology reports
Issue number5
Publication statusPublished - 2016 May


  • Anti-estrogen therapy
  • Breast cancer
  • Estrogen receptor
  • Estrogen response element
  • Metformin
  • Tamoxifen resistance

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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