Vitamin C and Endometrial Cancer

Epidemiological studies, linking vitamin C in reduced risk and treatment of endometrial cancer have been inclusive(1)(2).
Vitamin C, also known as L-ascorbic acid, is a water-soluble vitamin, found in fresh fruits, berries and green vegetables. It is best known for its free radical scavengers activity and regenerating oxidized vitamin E for immune support.

The University of Otago, may have found a link of  Low ascorbate levels and activation of increased activation of the HIF-1 pathway to endometrial cancer.Women wgo were disgnosed with endometrial cancer with low levels of ascorbate were found to have a elevated VEGF(a signal protein produced by cells that stimulates vasculogenesis and angiogenesis), GLUT-1(Expression levels of GLUT1 in cell membranes are increased by reduced glucose levels and decreased by increased glucose levels), and BNIP3(a potent inducer of autophagy in many cells) protein levels and with increased tumor size(3). Strong evidences also suggested that reactive oxygen species(ROS) are responsible for proteasome inhibitor-induced cell killing, vitamin C is found to  inhibit cell death through blocking the triggering proteasome inhibition(4). A combination including riboflavin, niacin and ascorbic acid, caused a significant decrease in the activity of glycolytic enzymes and a significant increase in the activities of gluconeogenic enzymes to near normal levels in experimental animals and may be considered as potential agent against tamoxifen mediated secondary endometrial carcinoma(5) and intake of vitamin C is associated to reduced risk of
endometrial cancer(6).
In secondary endometrial carcinoma bearing rat, the combination of  riboflavin, niacin and ascorbic acid exhibit their effects against tamoxifen mediated endometrial carcinoma, through a significant decrease in the activity of glycolytic enzymes(promoting continuous transport of glucose into the cell)(7). In a cultured human endometrial adenocarcinoma (AN3CA) cells, another combination of  application of sodium ascorbate (Vitamin C) and 2-methyl-1,4-naphthoquinone (Vitamin K3) stimulated cytotoxicity through the formation of reactive oxygen radicals, possibly accentuated by less defined secondary mechanisms(8). the syudy of the composition of ascorbic acid, pyruvic acid and the activity of malate dehydrogenase decarboxylizing (MDHD), also showed the increased reduced form of ascorbic and pyruvic acid in malignant growth(9).

Taking altogether, the combination of vitamin C and others may be associated to reduced risk and treatment of endometrial cancer through inhibition of cell cycle, and other mechanism such as decrease in the activity of glycolytic. Daily ingestion of high-dose vitamin C may be considered safe, but in rare incidence, overdoses in a prolonged period of time, may cause intra-renal oxalate crystal deposition, a fatal nephrotoxicity(10)(11).
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References
(1) Risk of endometrial cancer in relation to individual nutrients from diet and supplements by Biel RK¹, Csizmadi I, Cook LS, Courneya KS, Magliocco AM, Friedenreich CM.(PubMed)
(2) Nutritional factors in relation to endometrial cancer: a report from a population-based case-control study in Shanghai, China by Xu WH¹, Dai Q, Xiang YB, Zhao GM, Ruan ZX, Cheng JR, Zheng W, Shu XO.(PubMed)
(3) Low ascorbate levels are associated with increased hypoxia-inducible factor-1 activity and an aggressive tumor phenotype in endometrial cancer by Kuiper C¹, Molenaar IG, Dachs GU, Currie MJ, Sykes PH, Vissers MC(PubMed))
(4) Antioxidants block proteasome inhibitor function in endometrial carcinoma cells by Llobet D¹, Eritja N, Encinas M, Sorolla A, Yeramian A, Schoenenberger JA, Llombart-Cussac A, Marti RM, Matias-Guiu X, Dolcet X.(PubMed)
(5) Therapeutic potential of riboflavin, niacin and ascorbic acid on carbohydrate metabolizing enzymes in secondary endometrial carcinoma bearing rats by Sundravel S¹, Shanthi P, Sachdanandam P.(PubMed)
(6) Antioxidant vitamins and the risk of endometrial cancer: a dose-response meta-analysis.

Bandera EV¹, Gifkins DM, Moore DF, McCullough ML, Kushi LH(PubMed)
(7) Therapeutic potential of riboflavin, niacin and ascorbic acid on carbohydrate metabolizing enzymes in secondary endometrial carcinoma bearing rats by Sundravel S¹, Shanthi P, Sachdanandam P.(PubMed)
(8) Effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) treatment on human tumor cell growth in vitro. II. Synergism with combined chemotherapy action by De Loecker W¹, Janssens J, Bonte J, Taper HS.(PubMed)
(9) [Ascorbic, keto and hydroxy acid metabolism in the cell nuclei of certain tumors].[Article in Russian] by Romanovich EA, Basieva FI.(PubMed)
(10) Fatal vitamin C-associated acute renal failure by McHugh GJ, Graber ML, Freebairn RC.(PubMed)

(11) Ascorbic acid overdosing: a risk factor for calcium oxalate nephrolithiasis by Urivetzky M, Kessaris D, Smith AD.(PubMed)