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Monday, 17 February 2014

Prostate cancer in Vitamin C's Points of View

Kyle J. Norton

The widespread of prostate cancer, once considered a disease of aging male, now have become major concerns of governments and scientific community in South East Asian with tendency to effect even younger age population.

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.

Epidemiological studies, linking vitamin C in reduced risk and treatment of prostate cancer have produced inconsistent results.
In reviewed studies examined the relationship between prostate cancer and antioxidants indicated that there is no strong evidence for a beneficial effect of selenium, vitamin C, or beta-carotene, in reduced risk of prostate cancer and effect of dietary antioxidants on prostate cancer remains undefined and inconclusive(1). Supplemental vitamin C, in 1338 cases of prostate cancer among 29 361 men during up to 8 years of follow-up, also showed no strong support for high-dose antioxidant supplementation for the prevention of prostate cancer(2).
On Androgen-independent (DU145) and androgen-dependent (LNCaP) human prostate cancer cell lines, vitamin C inhibited prostate cancer cell proliferation through production of unidentified free radical(s) generation of hydrogen peroxide(3) and PC-3 through reactive oxygen specie(4) or through increased with temperature in cancer cells(5). Combination of Fe3O4@C nanoparticles (NPs) and Ascorbic acid (AA) enhanced cytotoxicity of PC-3 cells, through created hydroxyl radicals via an oxidative stress process(6). On intravenous (i.v.) vitamin C or ascorbic acid (ascorbate, vitamin C treatment depleted Adenosine triphosphate(ATP)(transports chemical energy within cells for metabolism) and induced autophagy in sensitive prostate cancer cells{(LaPC4)and  in five of the six tested prostate cancer cell lines}(7).
In a study of mixture of nutrients (NM) containing lysine, proline, ascorbic acid and green tea extract, showed that NM inhibited prostate cancer cell line PC-3 and DU-145 through suppression of the secretion of u-PA subunit 1(correlated with matrix proteolysis, cell adhesion, motility, and invasion)(8). Combination of Monensin and vitamin C study showed an enhancement of vitamin C in exhibition of the effect of  Monensin in induced apoptosis through increased generation of intracellular reactive oxygen species and by induction of a transcriptional profile characteristic of an oxidative stress response(9). In
redox-active form of vitamin C, ascorbate induced apoptosis through induction of cell cycle arrest(10).

Taking altogether, without going through the reviews, vitamin C may be effective in reduced risk and treatment of prostate cancer through generation of reactive oxygen species(ROS), or cell cycle arrest when used alone or combination with other chemo-agents or phytochmecials. 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(11)(22).



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References
(1) Dietary antioxidants and prostate cancer: a review by Vance TM, Su J, Fontham ET, Koo SI, Chun OK(PubMed)
(2) Supplemental and dietary vitamin E, beta-carotene, and vitamin C intakes and prostate cancer risk by Kirsh VA, Hayes RB, Mayne ST, Chatterjee N, Subar AF, Dixon LB, Albanes D, Andriole GL, Urban DA, Peters U; PLCO Trial(PubMed)
(3) Effect of vitamin C on prostate cancer cells in vitro: effect on cell number, viability, and DNA synthesis by Maramag C, Menon M, Balaji KC, Reddy PG, Laxmanan S(PubMed)
(4) Effect of vitamin C on androgen independent prostate cancer cells (PC3 and Mat-Ly-Lu) in vitro: involvement of reactive oxygen species-effect on cell number, viability and DNA synthesis by Menon M, Maramag C, Malhotra RK, Seethalakshmi L(PubMed)
(5) Peroxidase-like activity of Fe3O4@carbon nanoparticles enhances ascorbic acid-induced oxidative stress and selective damage to PC-3 prostate cancer cells by An Q, Sun C, Li D, Xu K, Guo J, Wang C.(PubMed)
(6) Effect of ascorbic acid on reactive oxygen species production in chemotherapy and hyperthermia in prostate cancer cells by Fukumura H, Sato M, Kezuka K, Sato I, Feng X, Okumura S, Fujita T, Yokoyama U, Eguchi H, Ishikawa Y, Saito T(PubMed)
(7) Pharmacological ascorbate induces cytotoxicity in prostate cancer cells through ATP depletion and induction of autophagy by Chen P, Yu J, Chalmers B, Drisko J, Yang J, Li B, Chen Q(PubMed)
(8) Down-regulation of urokinase plasminogen activator and matrix metalloproteinases and up-regulation of their inhibitors by a novel nutrient mixture in human prostate cancer cell lines PC-3 and DU-145 by Roomi MW, Kalinovsky T, Rath M, Niedzwiecki A(PubMed)
(9) Monensin is a potent inducer of oxidative stress and inhibitor of androgen signaling leading to apoptosis in prostate cancer cells by Ketola K, Vainio P, Fey V, Kallioniemi O, Iljin K(PubMed)
(10) Ascorbate exerts anti-proliferative effects through cell cycle inhibition and sensitizes tumor cells towards cytostatic drugs by Frömberg A, Gutsch D, Schulze D, Vollbracht C, Weiss G, Czubayko F, Aigner A(PubMed)

(11) Fatal vitamin C-associated acute renal failure by McHugh GJ, Graber ML, Freebairn RC.(PubMed)
(12) Ascorbic acid overdosing: a risk factor for calcium oxalate nephrolithiasis by Urivetzky M, Kessaris D, Smith AD.(PubMed)