Deuterium-depleted water inhibits the malignant progression of colorectal cancer cells by modulating oxidative stress

Colorectal cancer (CRC) is one of the most common types of cancer worldwide. Alternative therapy has been widely used in CRC treatment, with deuterium-depleted water (DDW) demonstrating promising anticancer effects in a number of cancer types. The aim of the present study was to assess the anticancer effects of DDW in CRC cells and the possible mechanism involved. HT-29 and DLD-1 cells were cultured in conditioned medium prepared with DDW. Cell malignant behaviors were assessed using EdU, colony formation, tumor-sphere formation, wound-healing and Transwell assays. Stemness-related proteins, Nanog and octamer-binding transcription factor-4, were assessed using western blotting. Intracellular reactive oxygen species (ROS) levels were determined using 2',7'-dichlorodihydrofluorescein diacetate fluorescent probes. Reverse transcription-quantitative PCR and western blotting were used to assess the expression of forkhead box protein M1 (FoxM1), cyclin D1 (CCND1) and matrix metalloproteinase 9 (MMP9). The results indicated that treatment with DDW significantly inhibited the proliferation, tumor-sphere formation, migration and invasion of HT-29 and DLD-1 cells, as well as the expression of stemness-related proteins. In the mechanistic analysis, DDW treatment was revealed to decrease ROS production and downregulate the expression of FoxM1. As the downstream targets of FoxM1, the expression levels of CCND1 and MMP9 were also shown to be decreased. Moreover, H₂O₂-induced oxidative stress rescued FoxM1 expression in the presence of DDW treatment, and overexpression of FoxM1 was demonstrated to abolish the DDW-mediated tumor suppressive effects. The findings from the present study indicate that the anticancer effects of DDW in CRC cells occur by inactivating the ROS/FoxM1 signaling pathway. Moreover, the results provide a possible agent for CRC treatment.