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

Abstract

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.

• Authors: Jinkyoung Kim, Jiyun Lee, Soon Young Jang, Chungyeul Kim, Yoojin Choi, Aeree Kim
• Journal: Oncology reports (Oncol Rep) Vol. 35 Issue 5 Pg. 2553-60 (May 2016) ISSN: 1791-2431 [Electronic] Greece
• PMID: 26986571 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Hormonal
• ESR1 protein, human
• Estrogen Receptor alpha
• Tamoxifen
• Estradiol
• Metformin

Topics

• Antineoplastic Agents, Hormonal (pharmacology)
• Breast Neoplasms (drug therapy, metabolism)
• Cell Proliferation (drug effects)
• Drug Resistance, Neoplasm
• Drug Synergism
• Estradiol (physiology)
• Estrogen Receptor alpha (metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Inhibitory Concentration 50
• MCF-7 Cells
• Metformin (pharmacology)
• Tamoxifen (pharmacology)
• Transcriptional Activation