Work

Natural compound rosmarinic acid displays anti-tumor activity in colorectal cancer cells by suppressing nuclear factor-kappa B signaling

Year: 2025

Type: article

Abstract: BACKGROUND: Rosmarinic acid (RA) is a natural polyphenol carboxylic acid known for its role in chemoprevention. Given its widespread use as a food additive, we are interested in whether RA affects the development of colorectal cancer (CRC). AIM: To examine the anti-tumor effects of RA on various CRC cell lines, and to further investigate the possible mechanisms. METHODS: Cell Counting Kit-8 assay and optical microscopy imaging were used to evaluate the viability of CRC cell lines. Western blot, quantitative real-time polymerase chain reaction, and flow cytometry analyses were performed to assess cell viability and activation of nuclear factor-kappa B (NF-κB) signaling. Molecular modeling was used to assess the interaction between RA and inhibitory kappa B kinase beta. Luciferase assay was used to examine the activity of NF-κB-driven transcription. The combinations of RA with 5-fluorouracil or oxaliplatin were utilized to evaluate the potential synergistic action of RA with the chemotherapeutics. RESULTS: RA exerted potent cytotoxic actions on all six CRC cell lines examined. RA was docked nicely into the binding pocket of inhibitory kappa B kinase beta by molecular modeling. The activity of NF-κB-driven luciferase and the phosphorylation of NF-κB p65 were decreased after exposure to the compound. Lipopolysaccharide-induced NF-κB activation was effectively inhibited by RA, too. Further, RA downregulated the expression of cell proliferation-related cyclin D1 and MYC, which are target genes of NF-κB. Of note, the cytotoxic actions of 5-fluorouracil and oxaliplatin were markedly enhanced by RA in those CRC cells. CONCLUSION: Our results indicate that RA inhibits NF-κB signaling and induces apoptosis in CRC cells. It enhances the cytotoxic actions of chemotherapeutics and might help to improve the chemotherapy of CRC.

Source: World Journal of Clinical Oncology

DOI: 10.5306/wjco.v16.i5.105341