In Vitro Studies
Numerous studies have demonstrated that pharmacological doses of ascorbic acid (0.1–100 mM) decrease cell proliferation in a variety of cancer cell lines.[1-5] Specifically, decreases in cell proliferation after ascorbic acid treatment have been reported for prostate, pancreatic,[7,8] hepatocellular, colon, mesothelioma, and neuroblastoma  cell lines.
The potential mechanisms through which treatment with high-dose ascorbic acid may exert its effects on cancer cells have been extensively investigated. Several studies have demonstrated that the in vitro direct cytotoxic effect of ascorbic acid on various types of cancer cells is mediated through a chemical reaction that generates hydrogen peroxide.[1,7] Reviewed in [13,14] Treating colon cancer cells with 2 mM to 3 mM of ascorbic acid resulted in downregulation of specificity protein (Sp) transcription factors and Sp-regulated genes involved in cancer progression. One study suggested that ascorbate-mediated prostate cancer cell death may occur through activation of an autophagy pathway.
Research has suggested that pharmacological doses of ascorbic acid enhance the effects of arsenic trioxide on ovarian cancer cells, gemcitabine on pancreatic cancer cells, and combination treatment of gemcitabine and epigallocatechin-3-gallate (EGCG) on mesothelioma cells.
However, not all studies combining vitamin C with chemotherapy have shown improved outcomes. Treating leukemia and lymphoma cells with dehydroascorbic acid (the oxidized form of vitamin C that increases levels of intracellular ascorbic acid) reduced the cytotoxic effects of various antineoplastic agents tested, including doxorubicin, methotrexate, and cisplatin (relative reductions in cytotoxicity ranged from 30% to 70%). In another study, multiple myeloma cells were treated with bortezomib and/or plasma obtained from healthy volunteers who had taken vitamin C supplements. Cells treated with a combination of bortezomib and volunteers’ plasma exhibited lower cytotoxicity than did cells treated with bortezomib alone.Animal Studies
Studies have demonstrated tumor growth inhibition after treatment with pharmacological ascorbate in animal models of pancreatic cancer,[1,7,8] liver cancer, prostate cancer, sarcoma, mesothelioma, and ovarian cancer.
The effects of high-dose ascorbic acid in combination with standard treatments on tumors have been investigated. In a mouse model of pancreatic cancer, the combination of gemcitabine (30 or 60 mg /kg every 4 days) and ascorbate (4 g /kg daily) resulted in greater decreases in tumor volume and weight, compared with gemcitabine treatment alone. According to a study reported in 2012, ascorbate enhanced the cancer cell–killing effects of photodynamic therapy in mice injected with breast cancer cells.
Using N-acetylcysteine (NAC) and vitamin C, researchers showed in 2007 that these compounds, both thought to act predominantly as antioxidants, may have antitumorigenic actions in vivo by decreasing levels of hypoxia -inducible factor (HIF)-1, a transcription factor that targets vascular endothelial growth factor (VEGF) and plays a role in angiogenesis.
There have also been reports of animal studies in which vitamin C has interfered with the anticancer activity of various drugs. In a study reported in 2008, administration of dehydroascorbic acid to lymphoma-xenograft mice prior to doxorubicin treatment resulted in significantly larger tumors than did treatment with doxorubicin alone. Treating multiple myeloma xenograft mice with a combination of oral vitamin C and bortezomib resulted in significantly greater tumor volume than did treatment with bortezomib alone.References
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- Heaney ML, Gardner JR, Karasavvas N, et al.: Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs. Cancer Res 68 (19): 8031-8, 2008. [PUBMED Abstract]
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