American Association for Cancer Research
15417786mcr190402-sup-220776_2_supp_5671382_pv89nw.doc (5.03 MB)

Supplementary Figures 1-7 from Targeting RNA Polymerase I with Hernandonine Inhibits Ribosomal RNA Synthesis and Tumor Cell Growth

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journal contribution
posted on 2023-04-03, 16:43 authored by Yen-Ting Chen, Jih-Jung Chen, Hsiang-Tsui Wang

S1. Hernandonine induces higher cytotoxicity and cellular apoptosis in HeLa and SAS cells. S2. Hernadonine induces rRNA polymerase I degradation, rRNA transcription, nucleolar cap and nucleolar disintegration in OECM-1. S3. Hernandonine induces p53-dependent and independent nucleolar stress pathways in HCT116 and OECM-1 cells. S4. Hernandonine induces expression of PUMA, but decreases expression of BCL-2 in HeLa and SAS cells. S5. Hernandonine induces nucleolar cap. S6. Hernandonine induces different cell fates in normal and cancer cells after recovery of treatment. S7. Higher dosage of hernandonine induces cellular apoptosis in NOK and Beas-2B cells.


Ministry of Science and Technology



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. Our findings position hernandonine as a potential, particular, and orally administered cancer treatment agent appropriate for use in investigational clinical trials.