beta-Escin overcomes trastuzumab resistance in HER2-positive breast cancer by targeting cancer stem-like featuresopen access
- Authors
- Park, Soeun; Park, Jung Min; Park, Minsu; Ko, Dongmi; Kim, Seongjae; Seo, Juyeon; Dal Nam, Kee; Jung, Eunsun; Farrand, Lee; Kim, Yoon-Jae; Kim, Ji Young; Seo, Jae Hong
- Issue Date
- 20-9월-2022
- Publisher
- BMC
- Keywords
- beta-escin; Trastuzumab resistance; Drug repurposing; p95HER2; HER2-positive breast cancer; Cancer stem cells
- Citation
- CANCER CELL INTERNATIONAL, v.22, no.1
- Indexed
- SCIE
SCOPUS
- Journal Title
- CANCER CELL INTERNATIONAL
- Volume
- 22
- Number
- 1
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/145741
- DOI
- 10.1186/s12935-022-02713-9
- ISSN
- 1475-2867
- 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.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.