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Targeting RNA Polymerase I with Hernandonine Inhibits Ribosomal RNA Synthesis and Tumor Cell Growth.

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.

Authors+Show Affiliations

Department of Pharmacology, National Yang-Ming University, Taipei, Taiwan.Faculty of Pharmacy, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.Department of Pharmacology, National Yang-Ming University, Taipei, Taiwan. htwang01@ym.edu.tw.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31409627

Citation

Chen, Yen-Ting, et al. "Targeting RNA Polymerase I With Hernandonine Inhibits Ribosomal RNA Synthesis and Tumor Cell Growth." Molecular Cancer Research : MCR, 2019.
Chen YT, Chen JJ, Wang HT. Targeting RNA Polymerase I with Hernandonine Inhibits Ribosomal RNA Synthesis and Tumor Cell Growth. Mol Cancer Res. 2019.
Chen, Y. T., Chen, J. J., & Wang, H. T. (2019). Targeting RNA Polymerase I with Hernandonine Inhibits Ribosomal RNA Synthesis and Tumor Cell Growth. Molecular Cancer Research : MCR, doi:10.1158/1541-7786.MCR-19-0402.
Chen YT, Chen JJ, Wang HT. Targeting RNA Polymerase I With Hernandonine Inhibits Ribosomal RNA Synthesis and Tumor Cell Growth. Mol Cancer Res. 2019 Aug 13; PubMed PMID: 31409627.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Targeting RNA Polymerase I with Hernandonine Inhibits Ribosomal RNA Synthesis and Tumor Cell Growth. AU - Chen,Yen-Ting, AU - Chen,Jih-Jung, AU - Wang,Hsiang-Tsui, Y1 - 2019/08/13/ PY - 2019/04/16/received PY - 2019/07/08/revised PY - 2019/08/08/accepted PY - 2019/8/15/pubmed PY - 2019/8/15/medline PY - 2019/8/15/entrez JF - Molecular cancer research : MCR JO - Mol. Cancer Res. N2 - 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. SN - 1557-3125 UR - https://www.unboundmedicine.com/medline/citation/31409627/Targeting_RNA_polymerase_I_with_hernandonine_inhibits_ribosomal_RNA_synthesis_and_tumor_cell_growth L2 - http://mcr.aacrjournals.org/cgi/pmidlookup?view=long&pmid=31409627 DB - PRIME DP - Unbound Medicine ER -