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Updated: Nov 27, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Antitumour activity of TH1579, a novel MTH1 inhibitor, against castration-resistant prostate cancer
Mingqiu Hu1, Jing Ning1, Likai Mao1
1Department of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233040, P.R. China.
Abstract:
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.
Insights
The MutT homolog 1 (MTH1) inhibitor TH1579 shows significant anti-tumor effects against castration-resistant prostate cancer (CRPC) cells. TH1579 effectively reduces CRPC cell proliferation and induces DNA damage, indicating its potential as a novel therapeutic agent.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Castration-resistant prostate cancer (CRPC) presents significant therapeutic challenges.
- Targeting key cellular pathways is crucial for developing effective CRPC treatments.
Purpose of the Study:
- To evaluate the anti-tumor efficacy of the MTH1 inhibitor TH1579 in CRPC models.
- To investigate the mechanisms underlying TH1579's anti-cancer activity.
Main Methods:
- Cell viability assays were performed on PC-3, DU-145, and C4-2 prostate cancer cell lines.
- Western blotting, immunofluorescence, and flow cytometry were used to assess DNA damage and apoptosis.
- Androgen receptor (AR) function was evaluated in C4-2 cells.
Main Results:
- TH1579 demonstrated dose-dependent inhibition of CRPC cell proliferation.
- TH1579 treatment led to increased 8-oxo-dG levels and DNA double-strand breaks.
- Increased 53BP1 and γH2A.X foci indicated significant DNA damage and apoptosis induction.
Conclusions:
- TH1579 exhibits potent anti-tumor activity against CRPC cells.
- The MTH1 inhibitor TH1579 shows promise as a potential therapeutic agent for CRPC treatment.
