COTI-2 suppresses the malignancy of bladder cancer by inducing apoptosis via the AMPK-mTOR signaling pathway.

Abstract

Objectives: COTI-2, an innovative oral homocysteine, has shown promising antitumor results on multiple types of cancer. However, its effects in treating bladder cancer (BCa) and the underlying molecular mechanisms have not been elucidated. The present study aimed to explore the antitumor effects of COTI-2 on BCa and the potential mechanisms.

Materials and methods: BCa cell lines, including the 5637 and T24 cell lines, were treated with COTI-2 at concentrations of 0.5 and 1 μM, respectively. Cell Counting Kit (CCK)-8 assay, colony formation assay, apoptosis assay, and transwell migration and invasion assay were conducted to evaluate the antitumor effects of COTI-2 on BCa cells. Western blotting, H&E, immunohistochemical staining, and immunofluorescence analysis were performed to investigate the underlying mechanisms. Moreover, a xenograft model in nude mice using T24 cells was generated to determine the antitumor activities of COTI-2 in vivo.

Results: COTI-2 highly inhibited the proliferation of BCa cell lines, including 5637 and T24 cells, and induced their apoptosis. Moreover, it efficiently suppressed the migration and invasion of BCa cells. Additionally, the subcutaneous xenograft model in nude mice showed that COTI-2 treatment inhibited the tumor growth of BCa by inducing its apoptosis in vivo. We also found that COTI-2 promoted apoptosis in BCa cells, presumably through activating the AMPK/mTOR pathway.

Conclusion: Our data suggest that COTI-2 effectively reduces the malignancy of BCa, probably by inducing apoptosis via the AMPK/mTOR signaling pathway. These data highlight the potential of COTI-2 as a therapeutic agent for the treatment of BCa.