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Tanshinone I suppresses hepatocellular carcinoma cells growth through targeting DNA double-strand break repair

Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors with increasing incidence rates and high mortality rates. The currently available methods for treating HCC include surgery, radiotherapy or chemotherapy, but all of them have limitations. Therefore, developing novel t...

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Detalles Bibliográficos
Autores principales: Qian, Zhen, Feng, Nannan, Geng, Anke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10324423/
https://www.ncbi.nlm.nih.gov/pubmed/37408176
http://dx.doi.org/10.1080/15384047.2023.2229958
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author Qian, Zhen
Feng, Nannan
Geng, Anke
author_facet Qian, Zhen
Feng, Nannan
Geng, Anke
author_sort Qian, Zhen
collection PubMed
description Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors with increasing incidence rates and high mortality rates. The currently available methods for treating HCC include surgery, radiotherapy or chemotherapy, but all of them have limitations. Therefore, developing novel therapeutic methods for HCC is in great need. Here, in this study, we found that tanshinone I, a small molecule compound, inhibited the proliferation of HCC cells in a dose-dependent manner. We also observed that Tanshinone I destabilized genomes by inhibiting both NHEJ and HR repair pathways, which are responsible for repairing DNA double strand breaks (DSBs). Mechanistically, this compound suppressed the expression of 53BP1, and the recruitment of RPA2 to DNA damage sites. Importantly, we demonstrated that combining Tanshinone I with radiotherapy exhibited better therapeutic potential for treating HCC.
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spelling pubmed-103244232023-07-07 Tanshinone I suppresses hepatocellular carcinoma cells growth through targeting DNA double-strand break repair Qian, Zhen Feng, Nannan Geng, Anke Cancer Biol Ther Research Paper Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors with increasing incidence rates and high mortality rates. The currently available methods for treating HCC include surgery, radiotherapy or chemotherapy, but all of them have limitations. Therefore, developing novel therapeutic methods for HCC is in great need. Here, in this study, we found that tanshinone I, a small molecule compound, inhibited the proliferation of HCC cells in a dose-dependent manner. We also observed that Tanshinone I destabilized genomes by inhibiting both NHEJ and HR repair pathways, which are responsible for repairing DNA double strand breaks (DSBs). Mechanistically, this compound suppressed the expression of 53BP1, and the recruitment of RPA2 to DNA damage sites. Importantly, we demonstrated that combining Tanshinone I with radiotherapy exhibited better therapeutic potential for treating HCC. Taylor & Francis 2023-07-05 /pmc/articles/PMC10324423/ /pubmed/37408176 http://dx.doi.org/10.1080/15384047.2023.2229958 Text en © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Research Paper
Qian, Zhen
Feng, Nannan
Geng, Anke
Tanshinone I suppresses hepatocellular carcinoma cells growth through targeting DNA double-strand break repair
title Tanshinone I suppresses hepatocellular carcinoma cells growth through targeting DNA double-strand break repair
title_full Tanshinone I suppresses hepatocellular carcinoma cells growth through targeting DNA double-strand break repair
title_fullStr Tanshinone I suppresses hepatocellular carcinoma cells growth through targeting DNA double-strand break repair
title_full_unstemmed Tanshinone I suppresses hepatocellular carcinoma cells growth through targeting DNA double-strand break repair
title_short Tanshinone I suppresses hepatocellular carcinoma cells growth through targeting DNA double-strand break repair
title_sort tanshinone i suppresses hepatocellular carcinoma cells growth through targeting dna double-strand break repair
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10324423/
https://www.ncbi.nlm.nih.gov/pubmed/37408176
http://dx.doi.org/10.1080/15384047.2023.2229958
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