REVIEW article
Front. Med.
Sec. Precision Medicine
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1633447
The Dual Role of Vitamin C in Cancer: From Antioxidant Prevention to Prooxidant Therapeutic Applications
Provisionally accepted
- 1Affiliated Hospital of Jiangsu University, Zhenjiang, China
- 2The first people's Hospital of Zhenjiang, Zhenjiang, China
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Vitamin C (VC), a pleiotropic molecule with context-dependent redox properties, exhibits dual roles in cancer biology through dose-dependent mechanisms. While nutritional VC intake demonstrates chemopreventive effects by scavenging carcinogen-induced reactive oxygen species (ROS) and maintaining genomic stability, high-dose intravenous VC acts as a prooxidant to selectively kill tumor cells via ROS-mediated deoxyribonucleic acid (DNA) damage, adenosine triphosphate (ATP) depletion, and HIF-1α degradation. Preclinical studies reveal VC's ability to reprogram the tumor microenvironment (TME) through collagen hydroxylation-mediated extracellular matrix remodeling, Treg suppression, and enhancement of CD8+ T cell infiltration. Importantly, VC synergizes with conventional therapies by radio-sensitizing hypoxic tumors through oxygen-sparing effects and reversing platinum resistance via glutathione depletion. Early-phase clinical trials corroborate VC's safety profile and potential to ameliorate chemotherapy-induced fatigue and nephrotoxicity. However, translational challenges persist, including the lack of pharmacokinetic standardization between oral and intravenous routes, tumor-type-specific response heterogeneity, and incomplete understanding of VC's immunomodulatory dynamics. Emerging strategies integrating VC with checkpoint inhibitors and TME-targeted nano-delivery systems show promise in preclinical models. This review synthesizes mechanistic insights from redox biology and immunometabolism to clinical trial data, proposing a framework for optimizing VC-based combination therapies while addressing critical gaps in biomarker development and dose scheduling. Deciphering the molecular determinants of VC's context-dependent anticancer effects may accelerate its rational clinical deployment.
Keywords: vitamin C, Ascorbic Acid, cancer prevention, cancer treatment, Tumor Microenvironment
Received: 22 May 2025; Accepted: 11 Aug 2025.
Copyright: © 2025 Cao, Yi, Ji, Liu, Wang and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yanfang Liu, The first people's Hospital of Zhenjiang, Zhenjiang, China
Dongqing Wang, Affiliated Hospital of Jiangsu University, Zhenjiang, China
Haitao Zhu, Affiliated Hospital of Jiangsu University, Zhenjiang, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.