한빛사논문
- 조회248
Ji Hyeon Kima,1, Jung Min Parkb,c,d,1, Eunsun Jungb,c,d, Jieun Leea, Jiyou Hane, Yoon-Jae Kimb,c,d, Ji Young Kimb,c,d, Jae Hong Seob,c,d, Jong Seung Kima
aDepartment of Chemistry, Korea University, Seoul, 02841, South Korea
bDivision of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul, 02841, South Korea
cBrain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Korea University, Seoul, 02841, South Korea
dDepartment of Biomedical Research Center, Korea University Guro Hospital, Korea University, Seoul, 08308, South Korea
eDepartment of Biological Sciences, Hyupsung University, Hwasung-si, 18330, South Korea
1Equally contributed.
Corresponding authors: Yoon-Jae Kim, Ji Young Kim, Jae Hong Seo, Jong Seung Kim
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.
논문정보
- Research article
- 2022년 10월 (BRIC 등록일 2022-11-18)
- 국내 연구진
- 의약학 > 종양의학
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