Antitumor effects of MutT homolog 1 inhibitors in human bladder cancer cells. Issue 12 (2nd December 2019)

• Record Type: Journal Article
• Authors: Lee, Jeong Woo; Lee, Sangchul; Ho, Jin-Nyoung; Youn, Je-In; Byun, Seok-Soo; Lee, Eunsik
• Is Part Of: Bioscience, biotechnology, and biochemistry. Volume 83:Issue 12(2019)
• Page Start: 2265
• Page End: 2271
• Publication Date: 2019-12-02
• Subjects: Bladder cancer -- cisplatin -- MutT homolog 1 -- drug resistance -- antitumor effect; Biotechnology -- Periodicals; Biochemistry -- Periodicals; 660.6
• DOI: 10.1080/09168451.2019.1648207
• Languages: English
• ISSNs: 0916-8451

Abstract

ABSTRACT: As 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 Graphical abstract: : Cell Counting Kit-8 assay in T24 and T24R2 bladder cancer cells treated with MTH1 inhibitors TH588 (A) and TH287 (B) for 24, 48, and 72 h. Asterisk indicates significant difference compared to control (P < 0.05).