Vitamin C and Cancer
James Meschino DC, MS, ROHP
Vitamin C has been shown to be an important agent in the adjunct management of cancer as in impacts a number of biological targets:
Inhibition of NF-kappa beta – Vitamin C has been shown to inactivate nuclear factor-B in endothelial cells during the inflammation process, independently of its antioxidant activity. As NF-kappa beta is involved in the inflammatory process as well as the proliferation of cancer cells, the anti-inflammatory activity of vitamin C may be mediated by multi-factorial mechanisms, which are not necessarily associated only with its intrinsic antioxidant activity.
Maintains Gap Junctions – As well, cell-to-cell communication through gap junction channels is essential for maintaining homeostatic balance through modulation of cell proliferation and differentiation in multicellular organisms. Inhibition of cell-to-cell communication is strongly related to the carcinogenic process, particularly to tumor promotion. Hydrogen peroxide, a well-known tumor promoter, also inhibits GJIC. Recently, we reported that vitamin C exerts protective effects against the disruption of GJIC by hydrogen peroxide.
An analysis by Rosenkranz et al, found that the inhibition of GJIC is strongly linked to the carcinogenic process, a biological phenomenon that may involve the inflammatory process, and to developmental effects in rodents. Integration of the analysis also suggests that the inhibition of GJIC is involved in nongenotoxic cancer induction and tumor promotion. Therefore, some experts suggest that the chemopreventive effects of vitamin C in carcinogenesis may be linked to the protective effects of vitamin C against epigenetic mechanisms, such as the inflammation and inhibition of GJIC, as well as to antioxidant activities. (1)
Induces Apoptosis In Cancer Cells – Vitamin C has been shown to upregulate caspase 3 enzyme in certain cancer cells, increasing apoptosis. Higher concentrations of vitamin C induce apoptotic cell death in various tumor cell lines including oral squamous cell carcinoma and salivary gland tumor cell lines (2). Kim et al showed that in human colon cancer cells vitamin C encouraged the phosphorylation of pro-apoptotic protein, Bad In addition, they also found that the vitamin C increased expression of pro-apoptotic protein, Bax and tumor suppressor gene product, p53, which usually resulted in apoptosis, in a time dependent manner. Moreover, they reported that vitamin C treatment disrupts mitochondrial membrane potential in HCT-8, human colon cancer cell line. Taken together, vitamin C has been shown to induce redox imbalance, resulting in apoptosis in human colon cancer cells by both endoplasmic reticulum stress and Bad/p53/Bax-mediated activation of mitochondrial pathway. (3)
Vitamin C and Immune Function – Vitamin C concentrations in the plasma and leukocytes rapidly decline during infections and stress. Supplementation of vitamin C was found to improve components of the human immune system such as antimicrobial and natural killer cell activities, lymphocyte proliferation, chemotaxis, and delayed-type hypersensitivity. Vitamin C contributes to maintaining the redox integrity of cells and thereby protects them against reactive oxygen species generated during the respiratory burst and in the inflammatory response. (4)
Supplemented dosages of vitamin C have also been shown to increase interferon levels, a factor that is important to the upregulation of death receptors on cancer cell, which may partially explain vitamin C-mediated apoptosis. (5)
1. Lee KW, Lee HJ, Surh YJ, Lee CY. Vitamin C and cancer chemoprevention:reappraisal. Am J Clin Nutr. 2003;78(6):1074-1078
2. Kang JS et al.Ascorbic acid (vitamin C) induces the apoptosis of B16 murine melanoma cells via a caspase-8–independent pathway. Cancer Immunology, Immunotherapy.2004;52(11):693-698.
3. Kim JE, Kang JS, JungDJ, Hahm E, Lee Sk et al. Vitamin C induces apoptosis in human colon cancer cells through endoplasmic reticulum stress and mitochondrial pathway. The Journal of Immunology.2007;178: 49.25.
4. Wintergers ES, Maggin S, Hornig DH. Annals of Nutrition and Metabolism 2006;50:85-94.
5. Thomas WR, Holt PG. Vitamin C and immunity: an assessment of the evidence. Clin Exp Immunol. 1978; 32(2): 370–379.