Chemoprevention is one of the ways to fight colorectal cancer, which is a huge challenge in oncology. Numerous pieces of evidence indicate that chronic inflammation in the course of Crohn’s disease or ulcerative colitis (UC) is a significant cancer risk factor. Epidemiologic studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs), including mesalazine, has beneficial effects on colitis-associated colorectal cancer. Mesalazine is a first-line therapy for UC and is also widely used for maintaining remission in UC. Data showed that mesalazine has antiproliferative properties associated with cyclooxygenase (COX) inhibition but can also act through COX-independent pathways. This review summarizes knowledge about mesalazine’s molecular mechanisms of action and chemopreventive effect by which it could interfere with colorectal cancer cell proliferation and survival.

Background/Objectives: Colorectal cancer (CRC) is one of the most common oncological disorders. Its fundamental treatments include surgery and chemotherapy, predominantly utilizing 5-fluorouracil (5-FU). Despite medical advances, CRC continues to present a high risk of recurrence, metastasis and low survival rates. Consequently, significant emphasis has been directed towards exploring novel types of cell death, particularly ferroptosis. Ferroptosis is characterized by iron imbalance and the accumulation of lipid peroxides and reactive oxygen species (ROS), leading to cellular damage and death. Thus, the discovery of safe inducers of ferroptosis, offering new hope in the struggle against CRC, remains crucial. In this study, we applied the concept of drug repositioning, selecting mesalazine (MES), a non-steroidal anti-inflammatory drug (NSAID), for investigation. Methods: The study was conducted on the colon cancer cell line DLD-1 and normal intestinal epithelial cells from the CCD 841 CoN cell line. Both cell lines were treated with MES solutions at concentrations of 10, 20, 30, 40, and 50 mM. Cytotoxicity was assessed using the MTT assay, while ferroptosis-related gene expression analysis was performed using oligonucleotide microarrays, with RT-qPCR used for validation. Results: MES effectively reduces the viability of DLD-1 cells while minimally affecting normal intestinal cells. Subsequent oligonucleotide microarray analysis revealed that MES significantly alters the expression of 56 genes associated with ferroptosis. Conclusions: Our results suggest that MES may induce ferroptosis in CRC, providing a foundation for further research in this area.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related deaths, meaning it is essential to explore all possible strategies for its prevention and treatment. Unfortunately, risk factors such as an unhealthy lifestyle, lack of exercise, and obesity—which are increasingly prevalent in developed countries—contribute to CRC development. The aim of this study was to evaluate the effect of a mesalazine (MES) and lactoferrin (LACT) combination on the viability of CRC cells and healthy intestinal epithelial cells, as well as to assess the expression profile of target genes within the Wnt/β-catenin pathway. Additionally, this study aimed to preliminarily analyze the mechanism of action underlying the combined effects of these compounds. In this study, we used three CRC cell lines (HCT-116, DLD-1, and HT-29) along with the healthy intestinal epithelial cell line CCD 841 CoN. These cells were treated with MES and LACT separately, as well as in combination. We demonstrated that the combination of MES and LACT reduced the viability of CRC cells more effectively than either compound alone, while slightly increasing the viability of normal intestinal epithelial cells. The synergistic effect of MES and LACT may serve as a foundation for developing new treatment strategies for CRC, utilizing compounds with a high safety profile.