{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T20:26:28Z","timestamp":1777321588646,"version":"3.51.4"},"reference-count":47,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T00:00:00Z","timestamp":1694217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["21K12261"],"award-info":[{"award-number":["21K12261"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["22K15288"],"award-info":[{"award-number":["22K15288"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["20231305"],"award-info":[{"award-number":["20231305"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fukuyama University","award":["21K12261"],"award-info":[{"award-number":["21K12261"]}]},{"name":"Fukuyama University","award":["22K15288"],"award-info":[{"award-number":["22K15288"]}]},{"name":"Fukuyama University","award":["20231305"],"award-info":[{"award-number":["20231305"]}]},{"name":"Cooperative Research Program of the Network Joint Research Center for Materials and Devices","award":["21K12261"],"award-info":[{"award-number":["21K12261"]}]},{"name":"Cooperative Research Program of the Network Joint Research Center for Materials and Devices","award":["22K15288"],"award-info":[{"award-number":["22K15288"]}]},{"name":"Cooperative Research Program of the Network Joint Research Center for Materials and Devices","award":["20231305"],"award-info":[{"award-number":["20231305"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>To identify effective treatment modalities for breast cancer with acquired resistance, we first compared the responsiveness of estrogen receptor-positive breast cancer MCF-7 cells and long-term estrogen-deprived (LTED) cells (a cell model of endocrine therapy-resistant breast cancer) derived from MCF-7 cells to G-1 and 2-methoxyestradiol (2-MeO-E2), which are microtubule-destabilizing agents and agonists of the G protein-coupled estrogen receptor 1 (GPER1). The expression of GPER1 in LTED cells was low (~0.44-fold), and LTED cells displayed approximately 1.5-fold faster proliferation than MCF-7 cells. Although G-1 induced comparable antiproliferative effects on both MCF-7 and LTED cells (IC50 values of &gt;10 \u00b5M), 2-MeO-E2 exerted antiproliferative effects selective for LTED cells with an IC50 value of 0.93 \u03bcM (vs. 6.79 \u03bcM for MCF-7 cells) and induced G2\/M cell cycle arrest. Moreover, we detected higher amounts of \u03b2-tubulin proteins in LTED cells than in MCF-7 cells. Among the \u03b2-tubulin (TUBB) isotype genes, the highest expression of TUBB2B (~3.2-fold) was detected in LTED cells compared to that in MCF-7 cells. Additionally, siTUBB2B restores 2-MeO-E2-mediated inhibition of LTED cell proliferation. Other microtubule-targeting agents, i.e., paclitaxel, nocodazole, and colchicine, were not selective for LTED cells. Therefore, 2-MeO-E2 can be an antiproliferative agent to suppress LTED cell proliferation.<\/jats:p>","DOI":"10.3390\/cimb45090464","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T10:48:28Z","timestamp":1694429308000},"page":"7336-7351","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["2-Methoxyestradiol as an Antiproliferative Agent for Long-Term Estrogen-Deprived Breast Cancer Cells"],"prefix":"10.3390","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5626-1950","authenticated-orcid":false,"given":"Masayo","family":"Hirao-Suzuki","sequence":"first","affiliation":[{"name":"Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hiro-koshingai, Kure-shi 737-0112, Hiroshima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koki","family":"Kanameda","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Life Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Sanzou 1, Gakuen-cho, Fukuyama-shi 729-0292, Hiroshima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7581-5314","authenticated-orcid":false,"given":"Masufumi","family":"Takiguchi","sequence":"additional","affiliation":[{"name":"Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hiro-koshingai, Kure-shi 737-0112, Hiroshima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0080-1476","authenticated-orcid":false,"given":"Narumi","family":"Sugihara","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Life Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Sanzou 1, Gakuen-cho, Fukuyama-shi 729-0292, Hiroshima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2193-1421","authenticated-orcid":false,"given":"Shuso","family":"Takeda","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Life Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Sanzou 1, Gakuen-cho, Fukuyama-shi 729-0292, Hiroshima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Early Breast Cancer Trialists\u2019 Collaborative Group (EBCTCG) (2015). 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