Antitumour activity of TH1579, a novel MTH1 inhibitor, against castration-resistant prostate cancer
Copyright: © Hu et al..
Castration-resistant prostate cancer (CRPC) treatment still remains difficult. The aim of the present study was to determine the antitumour efficacy of the MutT homolog 1 (MTH1) inhibitor, TH1579, against castration-resistant prostate cancer. PC-3 and DU-145 prostate cancer cells were treated with different concentrations of TH1579. C4-2 cells with or without androgen receptor (AR) were also treated with TH1579 to assess AR function. Cell survival, 8-oxo-dG levels and DNA damage were measured using cell viability assays, western blotting, immunofluorescence analysis and flow cytometry. TH1579 inhibited CRPC cell proliferation in a dose-dependent manner. The viabilities of PC-3 and DU-145 cells treated with 1 µM of TH1579 were 28.6 and 24.1%, respectively. The viabilities of C4-2 cells with and without AR treated with 1 µM TH1579 were 10.6 and 19.0%, respectively. Moreover, TH1579 treatment increased 8-oxo-dG levels, as well as the number of 53BP1 and γH2A.X foci, resulting in increased DNA double-strand breakage and apoptosis in PC-3 and DU-145 cells. The findings of the present study demonstrated that TH1579 exerted strong antitumour effects on CRPC cells, and may therefore be used as a potential therapeutic agent for the clinical treatment of CRPC.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2021 |
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Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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Enthalten in: |
Oncology letters - 21(2021), 1 vom: 14. Jan., Seite 62 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Hu, Mingqiu [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Revised 08.12.2020 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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doi: |
10.3892/ol.2020.12324 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM318478560 |
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520 | |a Castration-resistant prostate cancer (CRPC) treatment still remains difficult. The aim of the present study was to determine the antitumour efficacy of the MutT homolog 1 (MTH1) inhibitor, TH1579, against castration-resistant prostate cancer. PC-3 and DU-145 prostate cancer cells were treated with different concentrations of TH1579. C4-2 cells with or without androgen receptor (AR) were also treated with TH1579 to assess AR function. Cell survival, 8-oxo-dG levels and DNA damage were measured using cell viability assays, western blotting, immunofluorescence analysis and flow cytometry. TH1579 inhibited CRPC cell proliferation in a dose-dependent manner. The viabilities of PC-3 and DU-145 cells treated with 1 µM of TH1579 were 28.6 and 24.1%, respectively. The viabilities of C4-2 cells with and without AR treated with 1 µM TH1579 were 10.6 and 19.0%, respectively. Moreover, TH1579 treatment increased 8-oxo-dG levels, as well as the number of 53BP1 and γH2A.X foci, resulting in increased DNA double-strand breakage and apoptosis in PC-3 and DU-145 cells. The findings of the present study demonstrated that TH1579 exerted strong antitumour effects on CRPC cells, and may therefore be used as a potential therapeutic agent for the clinical treatment of CRPC | ||
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