Vitamin C Shows Promise in Treating Advanced Kidney Cancer:
Vitamin C, a vital nutrient known for its antioxidant, immune-boosting, and cosmetic benefits, has long been a subject of interest in cancer research. While its anti-tumor properties have been explored for years, the scientific community has remained divided, and the precise mechanisms by which Vitamin C may act against cancer—particularly metastatic renal cell carcinoma (RCC)—have remained elusive.
In a recent collaborative study, a team led by Professor Liqun Zhou and Professor Xuesong Li from the Department of Urology at Peking University First Hospital, together with Professor Weimin Ci from the General Hospital of the People’s Liberation Army, has shed new light on this issue. Their study, titled “Single-Cell Analysis Reveals that Vitamin C Inhibits Bone Metastasis of Renal Cancer via Cell Cycle Arrest and Microenvironment Remodeling,” was published in the prestigious journal Advanced Science (Q1, Impact Factor: 14.3). The research provides a comprehensive analysis of the therapeutic effects and underlying mechanisms of Vitamin C in the treatment of bone-metastatic kidney cancer.
Understanding Bone Metastasis in Kidney Cancer
Bone is the second most common site of metastasis in RCC after the lungs. Although targeted therapies and immunotherapies are available, outcomes remain poor and treatment is largely palliative. Bone metastasis is a highly complex process, driven by intricate interactions between the tumor cells and the bone marrow microenvironment. This dynamic is often explained by the “seed and soil” hypothesis, which suggests that certain tumor cells (seeds) have a proclivity for the bone marrow environment (soil).
Notably, bone metastasis is not the endpoint for tumor spread. Approximately two-thirds of patients with bone metastases eventually develop secondary metastases in other organs. Even when initial diagnosis reveals metastases in non-bone organs, micrometastases in the bone marrow are frequently present. These bone-residing tumor cells often exhibit cancer stem cell characteristics, potentially due to the hematopoietic stem cell-rich bone marrow niche, which fosters a strong “bone-homing” ability. This stem-like phenotype also enables tumor cells to evade immune detection by disguising themselves within the bone marrow milieu.
A deeper understanding of the tumor and microenvironmental features in bone-metastatic RCC is essential for developing effective treatments that can improve both survival and quality of life.
Research Highlights
In this study, researchers first successfully generated renal cancer stem cells using a 3D cell culture system. They then established an efficient mouse model of bone-metastatic RCC by injecting these cells via the tail artery. Transcriptomic analysis of the tumor stem cells revealed significant suppression of the Vitamin C pathway, prompting the researchers to hypothesize that supplementing with exogenous Vitamin C could have therapeutic potential.
Using both in vitro and in vivo approaches, the team administered a physiologically relevant dose of magnesium ascorbyl phosphate, a stable derivative of Vitamin C. The results were promising—Vitamin C significantly inhibited the proliferation of renal cancer stem cells and markedly reduced bone metastasis formation.
To further unravel the underlying mechanisms, the researchers performed single-cell RNA sequencing on tumor tissues from mice treated with Vitamin C compared to untreated controls. The findings revealed that Vitamin C induced cell cycle arrest in tumor cells, thereby curbing their proliferative capacity. Moreover, Vitamin C remodeled the tumor microenvironment in several important ways:
- It suppressed the differentiation of osteoclasts, mitigating bone destruction caused by metastasis.
- It modulated neutrophil recruitment, enhancing their cytotoxic activity.
- It downregulated the expression of CXCR2, leading to reduced infiltration of tumor-promoting N2-type neutrophils.
Strikingly, the combination of Vitamin C with a CXCR2 inhibitor further diminished bone metastasis formation, suggesting a synergistic effect.
Clinical Implications and Future Directions
This study is significant not only for identifying Vitamin C as a potential agent targeting cancer stem cells but also for highlighting its broader therapeutic potential in cancer treatment. The research supports the concept that Vitamin C, either alone or in combination with other drugs, could serve as a valuable adjunctive therapy for patients with RCC, especially those with bone metastases.
Authorship and Funding
Professor Liqun Zhou
Professor Xuesong Li
Dr. Gang Lin
Dr. Jianye Zhang
