Antitumour activity of TH1579, a novel MTH1 inhibitor, against castration‑resistant prostate cancer

Abstract

Castration‑resistant prostate cancer (CRPC) treat‑ ment 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.