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

backgroundRosmarinic 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).

aimTo examine the anti-tumor effects of RA on various CRC cell lines, and to further investigate the possible mechanisms.

methodsCell 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.

resultsRA 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.

conclusionOur 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.