4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) Targets Estrogen Receptor β, to Evoke the Resistance of Human Breast Cancer MCF-7 Cells to G-1, an Agonist for G Protein-Coupled Estrogen Receptor 1

Masayo Hirao-Suzuki; Keita Nagase; Tatsuya Suemori; Kana Tsutsumi; Egao Shigemori; Michitaka Tanaka; Masufumi Takiguchi; Narumi Sugihara; Shin’ichi Yoshihara; Shuso Takeda

doi:10.1248/bpb.b21-00417

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4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) Targets Estrogen Receptor β, to Evoke the Resistance of Human Breast Cancer MCF-7 Cells to G-1, an Agonist for G Protein-Coupled Estrogen Receptor 1

Masayo Hirao-Suzuki, Keita Nagase, Tatsuya Suemori, Kana Tsutsumi, Egao Shigemori, Michitaka Tanaka, Masufumi Takiguchi, Narumi Sugihara, Shin’ichi Yoshihara, Shuso Takeda

Author information

Masayo Hirao-Suzuki
Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University
Keita Nagase
Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University
Tatsuya Suemori
Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University
Kana Tsutsumi
Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University
Egao Shigemori
Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University
Michitaka Tanaka
Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University
Masufumi Takiguchi
Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University
Narumi Sugihara
Laboratory of Molecular Life Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
Shin’ichi Yoshihara
Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University
Shuso Takeda Corresponding author
Laboratory of Molecular Life Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University

Keywords: 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), bisphenol A (BPA), MCF-7, G protein-coupled estrogen receptor 1 (GPER1)

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2021 Volume 44 Issue 10 Pages 1524-1529

DOI https://doi.org/10.1248/bpb.b21-00417

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Abstract

Bisphenol A (BPA) has been shown to induce the activation of nuclear estrogen receptor α/β (ERα/β) in both in vitro and in vivo settings. We originally obtained a 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), a possible active metabolite of BPA, strongly activating the ERs-mediated transcription in MCF-7 cells with an EC₅₀ of 2.8 nM (i.e., BPA’s EC₅₀ = 519 nM). Environmental estrogens can also target G protein-coupled estrogen receptor 1 (GPER1), a membrane-type ER. However, the effects of BPA/MBP on GPER1, have not yet been fully resolved. In this study, we used MCF-7, a ERα/ERβ/GPER1-positive human breast cancer cell line, as a model to investigate the effects of the exposure to BPA or MBP. Our results revealed that at concentrations below 1 nM MBP, but not BPA, downregulates the expression of GPER1 mRNA via upregulated ERβ, and the MCF-7 cells pre-treated with MBP display resistance to GPER1 agonist G-1-mediated anti-proliferative effects. Because GPER1 can act as a tumor suppressor in several types of cancer including breast cancer, the importance of MBP-mediated decrease in GPER1 expression in breast cancer cells is discussed.

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