Antitumor effects of MutT homolog 1 inhibitors in human bladder cancer cells |
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| Authors: | Jeong Woo Lee Sangchul Lee Jin-Nyoung Ho Je-In Youn Seok-Soo Byun |
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| Affiliation: | 1. Department of Urology, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang-si, Korea;2. Department of Urology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Korea;3. Wide River Institute of Immunology, Seoul National University College of Medicine, Hongcheon, Korea |
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| Abstract: | ABSTRACTAs standard second-line regimen has not been established for patients who are refractory to or relapse with cisplatin-based chemotherapy, an effective class of novel chemotherapeutic agents is needed for cisplatin-resistant bladder cancer. Recent publications reported that MutT homolog 1 (MTH1) inhibitors suppress tumor growth and induce impressive therapeutic responses in a variety of human cancer cells. Few studies investigated the cytotoxic effects of MTH1 inhibitors in human bladder cancer. Accordingly, we investigated the antitumor effects and the possible molecular mechanisms of MTH1 inhibitors in cisplatin-sensitive (T24) and – resistant (T24R2) human bladder cancer cell lines. These results suggest that TH588 or TH287 may induce cancer cell suppression by off-target effects such as alterations in the expression of apoptosis- and cell cycle-related proteins rather than MTH1 inhibition in cisplatin-sensitive and – resistant bladder cancer cells.Abbreviations: MTH: MutT homolog; ROS: reactive oxygen species; CCK-8: cell counting kit-8; DCFH-DA: dichlorofluorescein diacetate; PARP: poly (ADP-ribose) polymerase |
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| Keywords: | Bladder cancer cisplatin MutT homolog 1 drug resistance antitumor effect |
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