Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Natural compound rosmarinic acid displays anti-tumor activity in colorectal cancer cells by suppressing nuclear factor-kappa B signaling
Wen-Yue Liu, Han Wang, Xin Xu, Xuan Wang, Kun-Kun Han, Wen-Dao You, Yili Yang, Tao Zhang
Wen-Yue Liu, Han Wang, Tao Zhang, Key Laboratory of Microecology-Immunomodulatory Network and Related Diseases, School of Basic Medicine, Jiamusi University, Jiamusi 154007, Heilongjiang Province, China
Wen-Yue Liu, Han Wang, Xin Xu, Xuan Wang, Kun-Kun Han, Yili Yang, China Regional Research Center, International Centre for Genetic Engineering and Biotechnology, Taizhou 225300, Jiangsu Province, China
Xin Xu, Kun-Kun Han, Yili Yang, Center for Self-Propelled Nanotechnologies, College of Biotechnology, Suzhou Industrial Park Institute of Services Outsourcing, Suzhou 215125, Jiangsu Province, China
Wen-Dao You, Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
Co-first authors: Wen-Yue Liu and Han Wang.
Co-corresponding authors: Yili Yang and Tao Zhang.
Author contributions: Yang Y and Zhang T conceived and designed the study, and reviewed and edited the manuscript; Liu WY, Wang H, Xu X, Wang X, Han KK, and You WD performed the experiments, and acquired and analyzed the data; Xu X and Han KK wrote the manuscript; Liu WY, Wang H, Xu X, Yang Y, and Zhang T revised and corrected the draft. Liu WY and Wang H are listed as co-first authors, who made equal contributions to this work. Yang Y and Zhang T are listed as co-corresponding authors, who contributed equally to this work. All authors have read and agreed to the published version of the manuscript.
Supported by Natural Science Foundation of Heilongjiang Province of China Under Grant, No. PL2024H020; and High-Quality Innovation Platform of Science and Education Innovation Zone in Suzhou Industrial Park-Key Platform Project, No. YZCXPT2023104.
Institutional review board statement: The study did not involve human or animal subjects.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Yili Yang, Professor, China Regional Research Center, International Centre for Genetic Engineering and Biotechnology, No. 8 Taohongjing Road, Taizhou 225300, Jiangsu Province, China.
nathanyang@icgeb.cn
Received: January 20, 2025
Revised: February 27, 2025
Accepted: March 24, 2025
Published online: May 24, 2025
Processing time: 120 Days and 13.5 Hours
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.
Core Tip: Given the widespread use of rosmarinic acid (RA) as a food additive, this study aimed to investigate whether RA affected colorectal cancer (CRC) development. We verified that RA exerted its anti-tumor activity through effectively suppressing nuclear factor-kappa B signaling, and enhanced the cytotoxic actions of 5-fluorouracil and oxaliplatin in CRC cells, which indicated that RA might help to improve the chemotherapy of CRC.
