Targeting RNA Polymerase I with Hernandonine Inhibits Ribosomal RNA Synthesis and Tumor Cell Growth.
Mol Cancer Res
; 17(11): 2294-2305, 2019 11.
Article
en En
| MEDLINE
| ID: mdl-31409627
ABSTRACT
RNA polymerase I (RNA Pol. I) activity is consistently expanded in multiplying cells to continue the expanded interest for ribosome generation and protein synthesis, which are fundamental for cell development and division. Thus, selective inhibitors of RNA Pol. I may offer a general helpful intends to block cancer cell multiplication. Hernandonine, isolated from the root wood of Hernandia nymphaeifolia, causes rearrangement of nucleolar proteins consistent with segregation of the nucleolus, a hallmark of RNA Pol. I transcription stress. Furthermore, the compound destabilizes RPA194, the large catalytic protein of RNA Pol. I, in a proteasome-dependent manner and inhibits nascent rRNA synthesis and expression of the 45S rRNA precursor. Finally, hernandonine induces cellular apoptosis through a p53-dependent or p53-independent process in solid tumor cell lines. These outcomes feature the prevailing effect of RNA Pol. I transcription stress on apoptosis pathway initiation and present a synthetically novel and significant molecule that represses RNA Pol. I, making it a potential objective for malignancy treatment. IMPLICATIONS Our findings position hernandonine as a potential, particular, and orally administered cancer treatment agent appropriate for use in investigational clinical trials.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Quinolinas
/
ARN Polimerasa I
/
ARN Ribosómico
/
Hernandiaceae
/
Compuestos Heterocíclicos de 4 o más Anillos
/
Antineoplásicos Fitogénicos
Límite:
Humans
Idioma:
En
Revista:
Mol Cancer Res
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2019
Tipo del documento:
Article
País de afiliación:
Taiwán