{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T21:12:38Z","timestamp":1780434758558,"version":"3.54.1"},"reference-count":58,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T00:00:00Z","timestamp":1633478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003621","name":"Ministry of Science ICT and Future Planning","doi-asserted-by":"publisher","award":["NRF-2018R1C1B6002803"],"award-info":[{"award-number":["NRF-2018R1C1B6002803"]}],"id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The survival rates for breast cancer (BC) have improved in recent years, but resistance, metastasis, and recurrence still remain major therapeutic challenges for BC. The acidic tumor microenvironment (TME) has attracted attention because of its association with tumorigenesis, metastasis, drug resistance, and immune surveillance. In this study, we evaluated natural compounds from traditional herbal medicine used to treat cancer that selectively target genes regulated by extracellular acidosis. We integrated four transcriptomic data including BC prognostic data from The Cancer Genome Atlas database, gene expression profiles of MCF-7 cells treated with 102 natural compounds, patterns of gene profiles by acidic condition, and single-cell RNA-sequencing from BC patient samples. Bruceine D (BD) was predicted as having the highest therapeutic potential, having an information gain (IG) score of 0.24, to regulate reprogrammed genes driven by acidosis affecting the survival of BC patients. BD showed the highest IG on EMT (IG score: 0.11) and invasion (IG score: 0.1) compared to the other phenotypes with the CancerSEA database. BD also demonstrated therapeutic potential by interfering with the tumor cell\u2013TME interactions by reducing the amyloid beta precursor protein and CD44 expression. Therefore, BD is a potential candidate to target the acidic TME induced metastatic process in BC.<\/jats:p>","DOI":"10.3390\/cells10102673","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T09:24:04Z","timestamp":1633598644000},"page":"2673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["In Silico Evaluation of Natural Compounds for an Acidic Extracellular Environment in Human Breast Cancer"],"prefix":"10.3390","volume":"10","author":[{"given":"YoungJoon","family":"Park","sequence":"first","affiliation":[{"name":"Cnh Center for Cancer Research, Cnh Corporation, Gangnam-gu, Seoul 06154, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaekwang","family":"Jeong","sequence":"additional","affiliation":[{"name":"Section of Endocrinology and Metabolism, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06519, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin","family":"Seong","sequence":"additional","affiliation":[{"name":"Soram Korean Medicine Hospital, Gangnam-gu, Seoul 06154, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonnam","family":"Kim","sequence":"additional","affiliation":[{"name":"Cnh Center for Cancer Research, Cnh Corporation, Gangnam-gu, Seoul 06154, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13014-020-01501-x","article-title":"Recent advances in radiotherapy of breast cancer","volume":"15","author":"Haussmann","year":"2020","journal-title":"Radiat. 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