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A synchronized dual drug delivery molecule targeting cancer stem cells in tumor heterogeneity and metastasis

Authors
Kim, Ji HyeonPark, Jung MinJung, EunsunLee, JieunHan, JiyouKim, Yoon-JaeKim, Ji YoungSeo, Jae HongKim, Jong Seung
Issue Date
Oct-2022
Publisher
Pergamon Press Ltd.
Keywords
Triple-negative breast cancer; Cancer stem cells; MDR1; Binary prodrug; Metastasis
Citation
Biomaterials, v.289
Indexed
SCIE
SCOPUS
Journal Title
Biomaterials
Volume
289
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/61522
DOI
10.1016/j.biomaterials.2022.121781
ISSN
0142-9612
Abstract
Cancer stem-like cells (CSCs) represent a key barrier to successful therapy for triple-negative breast cancer (TNBC). CSCs promote the emergence of chemoresistance, triggering relapse and resulting in a poor prognosis. We herein present CDF-TM, a new small molecule-based binary prodrug conjugated with SN-38 and 3,4-difluorobenzylidene curcumin (CDF) that is specifically activated in hypoxic conditions. CDF-TM treatment significantly induced apoptosis in TNBC-derived 3D spheroids, accompanied with caspase-3 activation as well as the attenuation of tumor stemness with evidence of reduction in aldehyde dehydrogenase 1 (ALDH1) activity and the CD44high/CD24low phenotype. An in vivo orthotopic allograft model was used to investigate its effects on tumor growth and metastasis. The dissemination of CSCs from primary allografts was impaired by CDF-TM, along with inhibition of tumor growth via eradication of CSCs and downregulation of multidrug resistance 1 (MDR1). This new small molecule-based binary prodrug offers a novel therapeutic option for metastatic TNBC.
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2. Clinical Science > Department of Medical Oncology and Hematology > 1. Journal Articles
3. Graduate School > Graduate School > 1. Journal Articles
4. Research institute > Cancer Institute > 1. Journal Articles

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