beta-Escin overcomes trastuzumab resistance in HER2-positive breast cancer by targeting cancer stem-like features
DC Field | Value | Language |
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dc.contributor.author | Park, Soeun | - |
dc.contributor.author | Park, Jung Min | - |
dc.contributor.author | Park, Minsu | - |
dc.contributor.author | Ko, Dongmi | - |
dc.contributor.author | Kim, Seongjae | - |
dc.contributor.author | Seo, Juyeon | - |
dc.contributor.author | Dal Nam, Kee | - |
dc.contributor.author | Jung, Eunsun | - |
dc.contributor.author | Farrand, Lee | - |
dc.contributor.author | Kim, Yoon-Jae | - |
dc.contributor.author | Kim, Ji Young | - |
dc.contributor.author | Seo, Jae Hong | - |
dc.date.accessioned | 2022-11-18T09:40:34Z | - |
dc.date.available | 2022-11-18T09:40:34Z | - |
dc.date.created | 2022-11-17 | - |
dc.date.issued | 2022-09-20 | - |
dc.identifier.issn | 1475-2867 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/145741 | - |
dc.description.abstract | Background: The emergence of de novo or intrinsic trastuzumab resistance is exceedingly high in breast cancer that is HER2 positive and correlates with an abundant cancer stem cell (CSC)-like population. We sought to examine the capacity of beta-escin, an anti-inflammatory drug, to address trastuzumab resistance in HER2-positive breast cancer cells. Methods: The effect of beta-escin on trastuzumab-resistant and -sensitive cell lines in vitro was evaluated for apoptosis, expression of HER2 family members, and impact on CSC-like properties. An in vivo model of trastuzumab-resistant JIMT-1 was used to examine the efficacy and toxicity of beta-escin. Results: beta-escin induced mitochondrial-mediated apoptosis accompanied by reactive oxygen species (ROS) production and increased active p18Bax fragmentation, leading to caspase-3/-7 activation. Attenuation of CSC-related features by beta-escin challenge was accompanied by marked reductions in CD44(high)/CD24(low) stem-like cells and aldehyde dehydrogenase 1 (ALDH1) activity as well as hindrance of mammosphere formation. beta-escin administration also significantly retarded tumor growth and angiogenesis in a trastuzumab-resistant JIMT-1 xenograft model via downregulation of CSC-associated markers and intracellular domain HER2. Importantly, beta-escin selectively inhibited malignant cells and was less toxic to normal mammary cells, and no toxic effects were found in liver and kidney function in animals. Conclusions: Taken together, our findings highlight beta-escin as a promising candidate for the treatment of trastuzumab-resistant HER2-positive breast cancers. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | BMC | - |
dc.subject | EPITHELIAL-MESENCHYMAL TRANSITION | - |
dc.subject | ALDEHYDE DEHYDROGENASE | - |
dc.subject | CELLS | - |
dc.subject | HER2 | - |
dc.subject | CLEAVAGE | - |
dc.subject | MARKER | - |
dc.subject | CD44 | - |
dc.subject | ROS | - |
dc.title | beta-Escin overcomes trastuzumab resistance in HER2-positive breast cancer by targeting cancer stem-like features | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Seo, Jae Hong | - |
dc.identifier.doi | 10.1186/s12935-022-02713-9 | - |
dc.identifier.scopusid | 2-s2.0-85138500565 | - |
dc.identifier.wosid | 000855817600001 | - |
dc.identifier.bibliographicCitation | CANCER CELL INTERNATIONAL, v.22, no.1 | - |
dc.relation.isPartOf | CANCER CELL INTERNATIONAL | - |
dc.citation.title | CANCER CELL INTERNATIONAL | - |
dc.citation.volume | 22 | - |
dc.citation.number | 1 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.subject.keywordPlus | EPITHELIAL-MESENCHYMAL TRANSITION | - |
dc.subject.keywordPlus | ALDEHYDE DEHYDROGENASE | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | HER2 | - |
dc.subject.keywordPlus | CLEAVAGE | - |
dc.subject.keywordPlus | MARKER | - |
dc.subject.keywordPlus | CD44 | - |
dc.subject.keywordPlus | ROS | - |
dc.subject.keywordAuthor | beta-escin | - |
dc.subject.keywordAuthor | Trastuzumab resistance | - |
dc.subject.keywordAuthor | Drug repurposing | - |
dc.subject.keywordAuthor | p95HER2 | - |
dc.subject.keywordAuthor | HER2-positive breast cancer | - |
dc.subject.keywordAuthor | Cancer stem cells | - |
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