The C-terminal HSP90 inhibitor NCT-58 kills trastuzumab-resistant breast cancer stem-like cells
- Authors
- Park, Soeun; Kim, Yoon-Jae; Park, Jung Min; Park, Minsu; Nam, Kee Dal; Farrand, Lee; Nguyen, Cong-Truong; La, Minh Thanh; Ann, Jihyae; Lee, Jeewoo; Kim, Ji Young; Seo, Jae Hong
- Issue Date
- 13-11월-2021
- Publisher
- SPRINGERNATURE
- Citation
- CELL DEATH DISCOVERY, v.7, no.1
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELL DEATH DISCOVERY
- Volume
- 7
- Number
- 1
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/135738
- DOI
- 10.1038/s41420-021-00743-2
- ISSN
- 2058-7716
- Abstract
- N-terminal HSP90 inhibitors in development have had issues arising from heat shock response (HSR) induction and off-target effects. We sought to investigate the capacity of NCT-58, a rationally-synthesized C-terminal HSP90 inhibitor, to kill trastuzumab-resistant HER2-positive breast cancer stem-like cells. NCT-58 does not induce the HSR due to its targeting of the C-terminal region and elicits anti-tumor activity via the simultaneous downregulation of HER family members as well as inhibition of Akt phosphorylation. NCT-58 kills the rapidly proliferating bulk tumor cells as well as the breast cancer stem-like population, coinciding with significant reductions in stem/progenitor markers and pluripotent transcription factors. NCT-58 treatment suppressed growth and angiogenesis in a trastuzumab-resistant xenograft model, concomitant with downregulation of ICD-HER2 and HSF-1/HSP70/HSP90. These findings warrant further investigation of NCT-58 to address trastuzumab resistance in heterogeneous HER2-positive cancers.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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