| Autor: |
Soeun Park, Yoon-Jae Kim, Jung Min Park, Minsu Park, Kee Dal Nam, Lee Farrand, Cong-Truong Nguyen, Minh Thanh La, Jihyae Ann, Jeewoo Lee, Ji Young Kim, Jae Hong Seo |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Cell Death Discovery, Vol 7, Iss 1, Pp 1-13 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2058-7716 |
| DOI: |
10.1038/s41420-021-00743-2 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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