Xu YY, Chen WJ, Cai YJ, Lin F, He ZP. Rosmarinic acid as a chemosensitizer in colorectal cancer: Targeting nuclear factor-kappa B pathway to overcome chemoresistance. World J Clin Oncol 2025; 16(8): 108279 [DOI: 10.5306/wjco.v16.i8.108279]
Corresponding Author of This Article
Zhi-Peng He, MD, PhD, Visiting Professor, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei 230000, Anhui Province, China. hezhipeng0901@163.com
Research Domain of This Article
Oncology
Article-Type of This Article
Editorial
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Aug 24, 2025; 16(8): 108279 Published online Aug 24, 2025. doi: 10.5306/wjco.v16.i8.108279
Rosmarinic acid as a chemosensitizer in colorectal cancer: Targeting nuclear factor-kappa B pathway to overcome chemoresistance
Yun-Yun Xu, Wen-Jing Chen, Yu-Jie Cai, Feng Lin, Zhi-Peng He
Yun-Yun Xu, Department of Obstetrics and Gynecology, Nanchang University, Nanchang 330031, Jiangxi Province, China
Wen-Jing Chen, Yu-Jie Cai, School of Pharmacy, Nanchang University, Nanchang 330031, Jiangxi Province, China
Feng Lin, Zhi-Peng He, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, Anhui Province, China
Co-first authors: Yun-Yun Xu and Wen-Jing Chen.
Co-corresponding authors: Feng Lin and Zhi-Peng He.
Author contributions: Xu YY and Chen WJ contributed equally to this manuscript as co-first authors of this manuscript; He ZP and Lin F equally conceptualized and drafted the first draft of the editorial, contributed to writing and editing the final draft of the manuscript, and as co-corresponding authors of this article; Xu YY, Chen WJ, and Cai YJ contributed to the discussion and conception of the manuscriptAll the authors critically revised and approved the final version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Zhi-Peng He, MD, PhD, Visiting Professor, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei 230000, Anhui Province, China. hezhipeng0901@163.com
Received: April 10, 2025 Revised: May 8, 2025 Accepted: June 30, 2025 Published online: August 24, 2025 Processing time: 132 Days and 23.7 Hours
Abstract
Colorectal cancer (CRC) is the third most common malignancy. However, the efficacy of current treatment strategies remains limited. In recent years, monomeric compounds from traditional Chinese medicine have received extensive attention in cancer therapy. Rosmarinic acid (RA), a natural phenolic acid, has multiple biological activities and exhibits anti-oncogenic effects in several cancers. Liu et al previously uncovered that RA could serve as a dual-action therapeutic agent in CRC. By suppressing nuclear factor-kappa B signaling via direct inhibition of inhibitory kappa B kinase beta, RA not only impedes tumor progression but also synergizes with first-line chemotherapeutics (5-fluorouracil/oxaliplatin) to reverse drug resistance. The authors demonstrate RA’s capacity to downregulate nuclear factor-kappa B-driven oncogenes and enhance chemotherapeutic cytotoxicity in vitro through integrative approaches, including molecular docking, luciferase assays, and functional validation. While these findings position RA as a cost-effective adjuvant in precision oncology, critical clinical translational gaps remain, including optimizing RA’s in vivo bioavailability, validating systemic safety in combinatorial regimens, and elucidating its immunomodulatory effects within the tumor microenvironment. This underscores the urgency of bridging phytochemistry and clinical oncology, advocating for biomarker-driven animal studies and phase I trials to translate RA’s potential into actionable CRC therapies. By addressing these hurdles, RA could emerge as a paradigm-shifting agent, harmonizing natural product efficacy with modern therapeutic precision.
Core Tip: This study demonstrates that rosmarinic acid (RA), a natural polyphenol, suppresses colorectal cancer progression by inhibiting nuclear factor-kappa B signaling and synergizes with chemotherapeutics (5-fluorouracil/oxaliplatin) to overcome drug resistance. RA’s dual role as a cytotoxic agent and chemosensitizer highlights its potential in precision oncology. While in vitro findings are promising, future research must address RA’s bioavailability, in vivo efficacy, and clinical safety to translate this natural compound into actionable colorectal cancer therapies.
