C Vitamini (Askorbik Asit)
Özet
C vitamini birçok enzimatik aktivite ve fizyolojik süreçte görevli, vücut için esansiyel bir vitamindir. İnsan vücudunda sentezi gerçekleştirilemediği için dışarıdan besinlerle ve takviyeler ile alınması zorunludur. Birçok hastalık ile C vitamini arasındaki ilişki iyi tanımlanmıştır ve bu nedenle de bu hastalıkların tedavisinde C vitamininin olası olumlu etkileri araştırılmaktadır. C vitamini ile kanser arasındaki ilişki de birçok çalışmanın konusunu oluşturmaktadır. Kanserin önlenmesi ve tedavisi konularında C vitamini ile yapılan çalışmalarda faydalarına dair birçok kanıt bulunmakla birlikte net bir fikir birliğine varılamamaktadır. Bu bölümde C vitamininin kanser gelişimi ile olan ilişkisi, kanser tedavisindeki yeri ve kanser tedavisinde kullanılan diğer ilaçlar ile etkileşimleri literatürdeki veriler gözden geçirilerek özetlenmeye çalışılmıştır.
Vitamin C is an essential vitamin for the body, involved in many enzymatic activities and physiological processes. Because of it can not be synthesized in the human body, it must be supplied by the diet and supplements. The relationship between many diseases and vitamin C is well defined and therefore the possible positive effects of vitamin C in the treatment of these diseases are being investigated. The relationship between vitamin C and cancer is the subject of many studies. There is a lot of evidence regarding the benefits of vitamin C in studies on cancer prevention and treatment but consensus is not reached. In this section, the relationship of vitamin C with cancer development, its place in cancer treatment, and its interactions with other drugs used in cancer treatment are tried to be summarized by reviewing the data in the literature.
Referanslar
Nishikimi M., Fukuyama R., Minoshima S., et al. Cloning and chromosomal mapping of the human nonfunctional gene for L-gulono-gamma-lactone oxidase, the enzyme for L-ascorbic acid biosynthesis missing in man. J. Biol. Chem. 1994;269:13685–13688. doi: 10.1016/S0021-9258(17)36884-9.
Lykkesfeldt J., Michels A.J., Frei B. Vitamin C. Adv. Nutr. 2014;5:16–18. doi: 10.3945/an.113.005157.
Padayatty SJ, Katz A, Wang Y, et al. Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr. (2003) 22:18–35. doi: 10.1080/07315724.2003.10719272
Roa F.J., Peña E., Gatica M., et al. Therapeutic use of vitamin C incancer:Physiologicalconsiderations. Front.Pharmacol. 2020;11:211. doi: 10.3389/fphar.2020.00211.
Carr A.C., McCall C. The role of vitamin C in the treatment of pain:Newinsights. J.Transl.Med. 2017;15:77.doi: 10.1186/s12967-017-1179-7.
Carr, A. C., & Maggini, S. (2017). Vitamin C and immune function. Nutrients, 9(11), 1211.
Bourne GH. The effect of vitamin C on healing wounds. Proc Nutr Soc. 1946;4:204.
Ball G.F.M. Vitamins: Their Role in the Human Body. 1st ed. Wiley-Blackwell; Hoboken, NJ, USA: 2004.
Cabanillas F. Vitamin C and cancer: What can we conclude—1609 patients and 33 years later? Puerto Rico Health Sci. J. 2010;29:215–217.
Vissers M.C.M., Das A.B. Potential mechanisms of action for vitamin C in cancer: Reviewing the evidence. Front. Physiol. 2018;9:809. doi: 10.3389/fphys.2018.00809.
Padayatty, S.J. ve Levine, M. (2001), “New insight into the physiology and pharmacology of vitamin C,” CMAJ., 164(3), 353-355.
Lawson, S. (2003), “The Trials and Tribulations of Vitamin C,” Journal of Orthomolecular Medicine, 18(3&4), 173-186.
Verrax, J., Taper, H. ve Calderon, P. (2008), “Targeting Cancer Cells by an Oxidant-Based Therapy,” Current Molecular Pharmacology, 1, 80-92.
Yun J, Rago C, Cheong I, Pagliarini R, et al. Glucose deprivation contributes to the development of KRAS pathway mutations in tumorcells. Science (2009) 325:15559.doi:10.1126/science.1174229
Alano CC, Garnier P, Ying W, et al. NAD+ depletion is necessary and sufficient for poly(ADP-ribose) polymerase-1-mediated neuronal death. J Neurosci (2010) 30:2967–78. doi: 10.1523/JNEUROSCI.5552-09.2010
Yun J, Mullarky E, Lu C, et al. Vitamin c selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science (2015) 350:1391–6. doi: 10.1126/science.aaa5004
Sagwal SK, Bekeschus S. ROS pleiotropy in melanoma and local therapy with physical modalities. Oxid Med Cell Longev (2021) 2021:6816214. doi: 10.1155/2021/6816214
Yang G, Yan Y, Ma Y, et al. Vitamin c at high concentrations induces cytotoxicity in malignant melanoma but promotes tumor growth at low concentrations. Mol Carcinog (2017) 56:1965–76. doi: 10.1002/mc.22654
Dang DT, Chen F, Gardner LB, et al. Hypoxia-inducible factor-1A promotes nonhypoxia-mediated proliferation in colon cancer cells and xenografts. Cancer Res (2006) 66:1684–693. doi: 10.1158/0008-5472.CAN-05-2887
Hukla SK, Purohit V, Mehla K, et al. MUC1 and HIF-1alpha signaling crosstalk induces anabolic glucose metabolism to impart gemcitabine resistance to pancreatic cancer. Cancer Cell (2017) 32:71–87.e7. doi: 10.1016/j.ccell.2017.06.004
Kuiper C, Dachs GU, Currie MJ, et al. Intracellular ascorbate enhances hypoxia-inducible factor (HIF)-hydroxylase activity and preferentially suppresses the HIF-1 transcriptional response. Free RadicBiolMed (2014) 69:30817.doi:10.1016/j.freeradbiomed.2014.01.033
Kuiper C, Dachs GU, Munn D, et al. Increased tumor ascorbate is associated with extended disease-free survival and decreased hypoxia-inducible factor-1 activation in human colorectal cancer. Front Oncol (2014) 4:10. doi: 10.3389/fonc.2014.00010
Chen C, Tang P, Yue J, et al. Effect of siRNA targeting HIF-1alpha combined l-ascorbate on biological behavior of hypoxic MiaPaCa2 cells. Technol Cancer Res Treat (2009) 8:235–40. doi: 10.1177/153303460900800309
Darvin P., Toor S.M., Sasidharan Nair V., et al. Immune checkpoint inhibitors: Recent progress and potential biomarkers. Exp. Mol. Med. 2018;50:1–11. doi: 10.1038/s12276-018-0191-1.
Rotte A. Combination of CTLA-4 and PD-1 blockers for treatment of cancer. J. Exp. Clin. Cancer Res. 2019;38:255. doi: 10.1186/s13046-019-1259-z.
Luchtel R.A., Bhagat T., Pradhan K., et al. High-dose ascorbic acid synergizes with anti-PD1 in a lymphoma mouse model. Proc. Natl.Acad.Sci.USA. 2020;117:1666,1677.doi: 10.1073/pnas.1908158117.
Cha J., Roomi M.W., Ivanov V., et al. Ascorbate supplementation inhibits growth and metastasis of B16FO melanoma and 4T1 breast cancer cells in vitamin C-deficient mice. Int. J. Oncol. 2013;42:55–64. doi: 10.3892/ijo.2012.1712.
Polireddy K, Dong R, Reed G, et al. High dose parenteral ascorbate inhibited pancreatic cancer growth and metastasis: mechanisms and a phase I/IIa study. Sci Rep (2017) 7:17188. doi: 10.1038/s41598-017-17568-8
Sajadian SO, Tripura C, Samani FS, et al. Vitamin c enhances epigenetic modifications induced by 5-azacytidine and cell cycle arrest in the hepatocellular carcinoma cell lines HLE and Huh7. Clin Epigenet (2016) 8:46. doi: 10.1186/s13148-016-0213-6
Zeng LH, Wang QM, Feng LY, et al. High-dose vitamin c suppresses the invasion and metastasis of breast cancer cells via inhibiting epithelial-mesenchymal transition. Onco Targets Ther (2019) 12:7405–13. doi: 10.2147/OTT.S222702
Cameron E., Campbell A. The orthomolecular treatment of cancer. II. Clinical trial of high-dose ascorbic acid supplements in advanced human cancer. Chem. Biol. Interact. 1974;9:285–315. doi: 10.1016/0009-2797(74)90019-2.
Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: prolongation of survival times in terminal human cancer. Proc Natl Acad Sci USA. 1976;73:3685–3689.
Murata A, Morishige F, Yamaguchi H. Prolongation of survival times of terminal cancer patients by administration of large doses of ascorbate. Int J Vit Nutr Res. 1982;2/23:103–113.
Nielsen, T.K.; Højgaard, M.; Andersen, J.T., et al. Weekly ascorbic acid infusion in castration-resistant prostate cancer patients: A single-arm phase II trial. Transl. Androl. Urol. 2017, 6, 517–528.
Hoffer L.J., Robitaille L., Zakarian R.,et al. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: A phase I-II clinical trial. PLoS ONE. 2015;10:e0120228. doi: 10.1371/journal.pone.0120228.
Block G. Vitamin C and cancer prevention: the epidemiologic evidence. Am J Clin Nutr. 1991;53(1):270S–282S.
Kushi LH, Fee RM, Sellers TA, et al. Intake of vitamins A, C, and E and postmenopausal breast cancer: The Iowa Women’s Health Study. Am J Epidemiol. 1996;144(2):165–174.
Hercberg S., Galan P., Preziosi P., et al. The SU.VI.MAX Study: A randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch. Intern. Med. 2004;164:2335–2342. doi: 10.1001/archinte.164.21.2335.
Stratton J., Godwin M. The effect of supplemental vitamins and minerals on the development of prostate cancer: A systematic review and meta-analysis. Fam. Pract. 2011;28:243–252. doi: 10.1093/fampra/cmq115.
Bai X., Qu X., Jiang X., et al. Association between dietary vitamin v Intake and risk of Prostate cancer: A meta-analysis involving 103,658Subjects. J.Cancer. 2015;6:913-921.doi: 10.7150/jca.12162.
Cho E., Hunter D.J., Spiegelman D., et al. Intakes of vitamins A, C and E and folate and multivitamins and lung cancer: A pooled analysis of 8 prospective studies. Int.J. Cancer. 2006;118:970–978. doi: 10.1002/ijc.21441.
Gandini S., Merzenich H., Robertson C., et al. Meta-analysis of studies on breast cancer risk and diet: The role of fruit and vegetable consumption and the intake of associated micronutrients. Eur.J.Cancer. 2000;36:636–646. doi: 10.1016/S0959-8049(00)00022-8.
Hu F., Jiang C., Wang Y.B., et al. Retinol, vitamins A, C, and E and breast cancer risk: A meta-analysis and meta-regression. Cancer Causes Control. 2011;22:1383–1396. doi: 10.1007/s10552-011-9811-y.
Pronsky ZM. Food-Medication Interactions. 11th ed2000.
Eslami M, Badkoubeh RS, Mousavi M, et al. Oral ascorbic acid in combination with beta-blockers is more effective than beta-blockers alone in the prevention of atrial fibrillation after coronary artery bypass grafting. Tex Heart Inst J. 2007;34(3):268-274.
Heaney ML, Gardner JR, Karasavvas N, et al. Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs. Cancer Res. Oct 1 2008;68(19):8031-8038.
Zeraati F. Et al., Ascorbic Acid Interaction With Analgesic Effect of Morphine and Tramadol in Mice. Anesth Pain Med. 2014 Aug; 4(3): e19529
Lykkesfeldt J., Michels A.J., Frei B. Vitamin C. Adv. Nutr. 2014;5:16–18. doi: 10.3945/an.113.005157.
Padayatty SJ, Katz A, Wang Y, et al. Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr. (2003) 22:18–35. doi: 10.1080/07315724.2003.10719272
Roa F.J., Peña E., Gatica M., et al. Therapeutic use of vitamin C incancer:Physiologicalconsiderations. Front.Pharmacol. 2020;11:211. doi: 10.3389/fphar.2020.00211.
Carr A.C., McCall C. The role of vitamin C in the treatment of pain:Newinsights. J.Transl.Med. 2017;15:77.doi: 10.1186/s12967-017-1179-7.
Carr, A. C., & Maggini, S. (2017). Vitamin C and immune function. Nutrients, 9(11), 1211.
Bourne GH. The effect of vitamin C on healing wounds. Proc Nutr Soc. 1946;4:204.
Ball G.F.M. Vitamins: Their Role in the Human Body. 1st ed. Wiley-Blackwell; Hoboken, NJ, USA: 2004.
Cabanillas F. Vitamin C and cancer: What can we conclude—1609 patients and 33 years later? Puerto Rico Health Sci. J. 2010;29:215–217.
Vissers M.C.M., Das A.B. Potential mechanisms of action for vitamin C in cancer: Reviewing the evidence. Front. Physiol. 2018;9:809. doi: 10.3389/fphys.2018.00809.
Padayatty, S.J. ve Levine, M. (2001), “New insight into the physiology and pharmacology of vitamin C,” CMAJ., 164(3), 353-355.
Lawson, S. (2003), “The Trials and Tribulations of Vitamin C,” Journal of Orthomolecular Medicine, 18(3&4), 173-186.
Verrax, J., Taper, H. ve Calderon, P. (2008), “Targeting Cancer Cells by an Oxidant-Based Therapy,” Current Molecular Pharmacology, 1, 80-92.
Yun J, Rago C, Cheong I, Pagliarini R, et al. Glucose deprivation contributes to the development of KRAS pathway mutations in tumorcells. Science (2009) 325:15559.doi:10.1126/science.1174229
Alano CC, Garnier P, Ying W, et al. NAD+ depletion is necessary and sufficient for poly(ADP-ribose) polymerase-1-mediated neuronal death. J Neurosci (2010) 30:2967–78. doi: 10.1523/JNEUROSCI.5552-09.2010
Yun J, Mullarky E, Lu C, et al. Vitamin c selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science (2015) 350:1391–6. doi: 10.1126/science.aaa5004
Sagwal SK, Bekeschus S. ROS pleiotropy in melanoma and local therapy with physical modalities. Oxid Med Cell Longev (2021) 2021:6816214. doi: 10.1155/2021/6816214
Yang G, Yan Y, Ma Y, et al. Vitamin c at high concentrations induces cytotoxicity in malignant melanoma but promotes tumor growth at low concentrations. Mol Carcinog (2017) 56:1965–76. doi: 10.1002/mc.22654
Dang DT, Chen F, Gardner LB, et al. Hypoxia-inducible factor-1A promotes nonhypoxia-mediated proliferation in colon cancer cells and xenografts. Cancer Res (2006) 66:1684–693. doi: 10.1158/0008-5472.CAN-05-2887
Hukla SK, Purohit V, Mehla K, et al. MUC1 and HIF-1alpha signaling crosstalk induces anabolic glucose metabolism to impart gemcitabine resistance to pancreatic cancer. Cancer Cell (2017) 32:71–87.e7. doi: 10.1016/j.ccell.2017.06.004
Kuiper C, Dachs GU, Currie MJ, et al. Intracellular ascorbate enhances hypoxia-inducible factor (HIF)-hydroxylase activity and preferentially suppresses the HIF-1 transcriptional response. Free RadicBiolMed (2014) 69:30817.doi:10.1016/j.freeradbiomed.2014.01.033
Kuiper C, Dachs GU, Munn D, et al. Increased tumor ascorbate is associated with extended disease-free survival and decreased hypoxia-inducible factor-1 activation in human colorectal cancer. Front Oncol (2014) 4:10. doi: 10.3389/fonc.2014.00010
Chen C, Tang P, Yue J, et al. Effect of siRNA targeting HIF-1alpha combined l-ascorbate on biological behavior of hypoxic MiaPaCa2 cells. Technol Cancer Res Treat (2009) 8:235–40. doi: 10.1177/153303460900800309
Darvin P., Toor S.M., Sasidharan Nair V., et al. Immune checkpoint inhibitors: Recent progress and potential biomarkers. Exp. Mol. Med. 2018;50:1–11. doi: 10.1038/s12276-018-0191-1.
Rotte A. Combination of CTLA-4 and PD-1 blockers for treatment of cancer. J. Exp. Clin. Cancer Res. 2019;38:255. doi: 10.1186/s13046-019-1259-z.
Luchtel R.A., Bhagat T., Pradhan K., et al. High-dose ascorbic acid synergizes with anti-PD1 in a lymphoma mouse model. Proc. Natl.Acad.Sci.USA. 2020;117:1666,1677.doi: 10.1073/pnas.1908158117.
Cha J., Roomi M.W., Ivanov V., et al. Ascorbate supplementation inhibits growth and metastasis of B16FO melanoma and 4T1 breast cancer cells in vitamin C-deficient mice. Int. J. Oncol. 2013;42:55–64. doi: 10.3892/ijo.2012.1712.
Polireddy K, Dong R, Reed G, et al. High dose parenteral ascorbate inhibited pancreatic cancer growth and metastasis: mechanisms and a phase I/IIa study. Sci Rep (2017) 7:17188. doi: 10.1038/s41598-017-17568-8
Sajadian SO, Tripura C, Samani FS, et al. Vitamin c enhances epigenetic modifications induced by 5-azacytidine and cell cycle arrest in the hepatocellular carcinoma cell lines HLE and Huh7. Clin Epigenet (2016) 8:46. doi: 10.1186/s13148-016-0213-6
Zeng LH, Wang QM, Feng LY, et al. High-dose vitamin c suppresses the invasion and metastasis of breast cancer cells via inhibiting epithelial-mesenchymal transition. Onco Targets Ther (2019) 12:7405–13. doi: 10.2147/OTT.S222702
Cameron E., Campbell A. The orthomolecular treatment of cancer. II. Clinical trial of high-dose ascorbic acid supplements in advanced human cancer. Chem. Biol. Interact. 1974;9:285–315. doi: 10.1016/0009-2797(74)90019-2.
Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: prolongation of survival times in terminal human cancer. Proc Natl Acad Sci USA. 1976;73:3685–3689.
Murata A, Morishige F, Yamaguchi H. Prolongation of survival times of terminal cancer patients by administration of large doses of ascorbate. Int J Vit Nutr Res. 1982;2/23:103–113.
Nielsen, T.K.; Højgaard, M.; Andersen, J.T., et al. Weekly ascorbic acid infusion in castration-resistant prostate cancer patients: A single-arm phase II trial. Transl. Androl. Urol. 2017, 6, 517–528.
Hoffer L.J., Robitaille L., Zakarian R.,et al. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: A phase I-II clinical trial. PLoS ONE. 2015;10:e0120228. doi: 10.1371/journal.pone.0120228.
Block G. Vitamin C and cancer prevention: the epidemiologic evidence. Am J Clin Nutr. 1991;53(1):270S–282S.
Kushi LH, Fee RM, Sellers TA, et al. Intake of vitamins A, C, and E and postmenopausal breast cancer: The Iowa Women’s Health Study. Am J Epidemiol. 1996;144(2):165–174.
Hercberg S., Galan P., Preziosi P., et al. The SU.VI.MAX Study: A randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch. Intern. Med. 2004;164:2335–2342. doi: 10.1001/archinte.164.21.2335.
Stratton J., Godwin M. The effect of supplemental vitamins and minerals on the development of prostate cancer: A systematic review and meta-analysis. Fam. Pract. 2011;28:243–252. doi: 10.1093/fampra/cmq115.
Bai X., Qu X., Jiang X., et al. Association between dietary vitamin v Intake and risk of Prostate cancer: A meta-analysis involving 103,658Subjects. J.Cancer. 2015;6:913-921.doi: 10.7150/jca.12162.
Cho E., Hunter D.J., Spiegelman D., et al. Intakes of vitamins A, C and E and folate and multivitamins and lung cancer: A pooled analysis of 8 prospective studies. Int.J. Cancer. 2006;118:970–978. doi: 10.1002/ijc.21441.
Gandini S., Merzenich H., Robertson C., et al. Meta-analysis of studies on breast cancer risk and diet: The role of fruit and vegetable consumption and the intake of associated micronutrients. Eur.J.Cancer. 2000;36:636–646. doi: 10.1016/S0959-8049(00)00022-8.
Hu F., Jiang C., Wang Y.B., et al. Retinol, vitamins A, C, and E and breast cancer risk: A meta-analysis and meta-regression. Cancer Causes Control. 2011;22:1383–1396. doi: 10.1007/s10552-011-9811-y.
Pronsky ZM. Food-Medication Interactions. 11th ed2000.
Eslami M, Badkoubeh RS, Mousavi M, et al. Oral ascorbic acid in combination with beta-blockers is more effective than beta-blockers alone in the prevention of atrial fibrillation after coronary artery bypass grafting. Tex Heart Inst J. 2007;34(3):268-274.
Heaney ML, Gardner JR, Karasavvas N, et al. Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs. Cancer Res. Oct 1 2008;68(19):8031-8038.
Zeraati F. Et al., Ascorbic Acid Interaction With Analgesic Effect of Morphine and Tramadol in Mice. Anesth Pain Med. 2014 Aug; 4(3): e19529
Sayfalar
399-404
Yayınlanan
11 Mart 2024
Telif Hakkı (c) 2024 Akademisyen Yayınevi Kitap Portalı
Lisans
LisansNasıl Atıf Yapılır
1.
Günaltılı M. C Vitamini (Askorbik Asit). Içinde: Sakin A, editör. Kanser Hastalarının Başvurduğu Geleneksel ve Tamamlayıcı Tedaviler - Tıbbi Onkolog Gözü ile Bakış ve Onkolojik İlaçlarla Etkileşim [Internet]. Türkiye: Akademisyen Yayınevi Kitap DOI Portalı; 2024 [a.yer 13 Temmuz 2026]. ss. 399-404. Erişim adresi: https://omp35.books.akademisyen.net/index.php/akya/catalog/book/2380/chapter/13976
