Studies of Anticancer Activity of Beta-carotene, Alpha-tocopherol and Ascorbic acid in SH-SY5Y Neuroblastoma Cells

Abstract

Neuroblastoma (NB; SH-SY5Y cells) is important characteristic of the most widespread cancer in children after leukaemia and brain cancer. Discovery of new treatment approaches are required for NB disease. Epidemiological studies have demonstrated that different types of antioxidants are associated with decreased cancer and neurodegenerative diseases. Fruits and vegetables have a plenty source of Beta-carotene (BC), Alpha-tocopherol (vit E) and Ascorbic acid (vit C) that have potent free radicals scavenging actions and inhibitory properties to biochemical oxidation. BC, vit E and vit C increase the intracellular reactive oxygen species (ROS) generation and encourages cell apoptosis. It was found that these antioxidants resulted in an increase in the malondialdehyde (MDA) (marker of lipid peroxidation; LPO) and ROS levels at high concentration suggesting it behaves as a prooxidant in this study. The outcomes obviously indicated that studies of SH-SY5Y with dose-dependent BC, vit E and vit C results in oxidative damage through an increase in ROS and LPO generation and the expression of apoptotic marker caspase-3. These consequences find out additional evidences that these antioxidants could be involved in the process of apoptosis for new therapy in NB cells.

Keywords

• Beta carotene,alpha tocopherol,ascorbic acid,apoptosis,SH-SY5Y

SH-SY5Y Nöroblastom Hücrelerinde Beta-karoten, Alfa-tokoferol ve Askorbik asidin Antikanser Etkilerinin Araştırılması

Abstract

Nöroblastom (NB; SH-SY5Y hücreleri), lösemi ve beyin kanserinden sonra özellikle çocuklarda en yaygın görülen kanser türü olduğu için çalışılması tercih edilmiştir. NB için yeni tedavi yaklaşımları gerekmektedir. Bazı ülkelerde yapılan epidemiyolojik çalışmalar, farklı tipte antioksidanların kanser ve nörodejeneratif hastalıkların azalması ile ilişkili olduğunu göstermektedir. Meyve ve sebzeler, biyokimyasal oksidasyonu engelleyici etkileri ve serbest radikalleri yakalama özellikleri olan bol miktarda Beta-karoten (BC), Alfa-tokoferol (vit E) ve Askorbik asit (vit C) içermektedir. BC, vit E ve vit C hücre içi ROS oluşumunu arttırarak apoptozu teşvik edebilmektedir. Bazı çalışmalarda belirtildiği üzere bu antioksidanların yüksek konsantrasyonlarda, LPO ve ROS oluşumunda bir artışa yol açtığı ve prooksidan olarak davrandığı gösterilmektedir. Bu çalışmanın sonucunda elde edilen veriler, BC, vit E ve vit C’nin SH-SY5Y NB hücreleri üzerindeki etkisi doza bağımlı olarak ROS ve LPO üretiminde bir artışa sebep olarak oksidatif hasara ve devamında apoptotik kaspaz-3 proteini ekspresyonunda artışa neden olduğunu açıkça göstermektedir. Elde edilen sonuçlar, bu çalışmada etkisi araştırılan antioksidanların NB hücreleri için apoptoz sürecinde yeni tedavi yaklaşımları açısından değerlendirilebileceğini göstermektedir.

Keywords

• Beta-karoten,alfa-tokoferol,askorbik asit,apoptoz,SH-SY5Y

References

1. Abraham A, Kattoor AJ, Saldeen T, Mehta JL, 2018. Vitamin E and its anticancer effects. Critical reviews in food science and nutrition, 1-8.
2. Agholme L, Lindström T, Kågedal K, Marcusson, J, Hallbeck M, 2010. An in vitro model for neuroscience: differentiation of SH-SY5Y cells into cells with morphological and biochemical characteristics of mature neurons. Journal of Alzheimer's disease, 20(4): 1069-1082.
3. Bayindir S, Ayna A, Temel Y, Ciftci M, 2018. The synthesis of new oxindoles as analogs of natural product 3, 3'-bis (indolyl) oxindole and in vitro evaluation of the enzyme activity of G6PD and 6PGD. Turkish Journal of Chemistry, 42(2), 332-345.
4. Bendich A, 1989. Carotenoids and the immune response. The Journal of Nutrition, 119: 112-15.
5. Bjorneboe A, Bjørneboe GEA, Drevon CA, 1990. Absorption, transport and distribution of vitamin E. The Journal of Nutrition, 120(3): 233-242.
6. Bogenmann E, 1996. A metastatic neuroblastoma model in SCID mice. International Journal of Cancer, 67(3): 379-385.
7. Burton GW, Joyce A, Ingold KU, 1983. Is vitamin E the only lipid-soluble, chain-breaking antioxidant in human blood plasma and erythrocyte membranes. Archives of Biochemistry and Biophysics, 221(1): 281-290.
8. Byers T, Perry G, 1992. Dietary carotenes, vitamin C, and vitamin E as protective antioxidants in human cancers. Annual Review of Nutrition, 12(1): 139-159.

9. Cui Y, Lu Z, Bai L, Shi Z, Zhao WE, Zhao B, 2007. β-Carotene induces apoptosis and up-regulates peroxisome proliferator-activated receptor γ expression and reactive oxygen species production in MCF-7 cancer cells. European Journal of Cancer, 43(17): 2590-2601.
10. Darendelioglu E, Aykutoglu G, Tartik M, Baydas G, 2016. Turkish propolis protects human endothelial cells in vitro from homocysteine-induced apoptosis. Actahistochemica, 118(4): 369-376.
11. Frei B, England L, Ames BN, 1989. Ascorbate is an outstanding antioxidant in human blood plasma. Proceedings of the National Academy of Sciences, 86(16): 6377-6381.
12. Grosso G, Buscemi S, Galvano F, Mistretta A, Marventano S, La Vela V, Biondi A, 2013. Mediterranean diet and cancer: epidemiological evidence and mechanism of selected aspects. BMC surgery, 13(2): 14.
13. Hazuka MB, Edwards-Prasad J, Newman F, Kinzie JJ, Prasad KN, 1990. Beta-carotene induces morphological differentiation and decreases adenylate cyclase activity in melanoma cells in culture. Journal of the American College of Nutrition, 9(2): 143-149.
14. Henson DE, Block G, Levine M, 1991. Ascorbic acid: biologic functions and relation to cancer. JNCI: Journal of the National Cancer Institute, 83(8): 547-550.
15. Horrobin DF, 1991. Is the main problem in free radical damage caused by radiation, oxygen and other toxins the loss of membrane essential fatty acids rather than the accumulation of toxic materials. Medical hypotheses, 35(1): 23-26.
16. Horvath PM, Ip C, 1983. Synergistic effect of vitamin E and selenium in the chemoprevention of mammary carcinogenesis in rats. Cancer research, 43(11): 5335-5341.
17. Ip C, 1982. Dietary vitamin E intake and mammary carcinogenesis in rats. Carcinogenesis, 3(12): 1453-1456.
18. Jämsä A, Hasslund K, Cowburn RF, Bäckström A, Vasänge M, 2004. The retinoic acid and brain-derived neurotrophic factor differentiated SH-SY5Y cell line as a model for Alzheimer’s disease-like tau phosphorylation. Biochemical and Biophysical Research Communications, 319(3): 993-1000.
19. Jiang M, Stanke J, Lahti JM, 2011. The connections between neural crest development and neuroblastoma.In Current topics in developmental biology. Academic Press, 94: 77-127.
20. Kahl R, Kampkötter A, Wätjen W, Chovolou Y, 2004. Antioxidant enzymes and apoptosis. Drug metabolism reviews, 36(3-4): 747-762.
21. Kavalappa YP, Rudresh DU, Gopal SS, Shivarudrappa AH, Stephen NM, Rangiah K, Ponesakki G, 2019. β-carotene isolated from the marine red alga, Gracillaria sp. potently attenuates the growth of human hepatocellular carcinoma (HepG2) cells by modulating multiple molecular pathways. Journal of Functional Foods, 52, 165-176.
22. Knekt P, Aromaa A, Maatela J, Aaran RK, Nikkari T, Hakama M, Teppo L, 1991. Vitamin E and cancer prevention. The American Journal of Clinical Nutrition, 53(1): 283-286.
23. Kolankaya D, Selmanoǧlu G, Sorkun K, Salih B, 2002. Protective effects of Turkish propolis on alcohol-induced serum lipid changes and liver injury in male rats. Food Chemistry, 78(2): 213-217.
24. Koriyama Y, Furukawa A, Muramatsu M, Takino JI., Takeuchi M, 2015. Glyceraldehyde caused Alzheimer’s disease-like alterations in diagnostic marker levels in SH-SY5Y human neuroblastoma cells. Scientific Reports, 5: 13313.
25. Lin J, Cook NR, Albert C, Zaharris E, Gaziano JM, Van Denburgh M, Manson JE, 2009. Vitamins C and E and beta carotene supplementation and cancer risk: a randomized controlled trial. Journal of the National Cancer Institute, 101(1): 14-23.
26. Maris JM, 2010. Recent advances in neuroblastoma. New England Journal of Medicine, 362(23): 2202-2211.
27. Maris JM, Hogarty MD, Bagatell R, Cohn SL, 2007. Neuroblastoma.The Lancet 369 (9579): 2106–2120.
28. Mazerand C, Cock IE, 2019. An Examination of the Antibacterial, Antifungal, Anti-Giardial and Anticancer Properties of Buchanania obovata Engl. Fruit Extracts. Pharmacognosy Communications, 9(1).
29. Middha P, Weinstein SJ, Männistö S, Albanes D, Mondul AM, 2018. β-Carotene Supplementation and Lung Cancer Incidence in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study: The Role of Tar and Nicotine. Nicotine & Tobacco Research.
30. Palozza P, Serini S, Maggiano N, Angelini M, Boninsegna A, Di Nicuolo F, Calviello G, 2002. Induction of cell cycle arrest and apoptosis in human colon adenocarcinoma cell lines by β-carotene through down-regulation of cyclin A and Bcl-2 family proteins. Carcinogenesis, 23(1): 11-18.
31. Palozza P, Serini S, Torsello A, Di Nicuolo F, Piccioni E, Ubaldi V, Calviello G, 2003. β-Carotene regulates NF-κB DNA-binding activity by a redox mechanism in human leukemia and colon adenocarcinoma cells. The Journal of Nutrition, 133(2): 381-388.
32. Pastorino U, Pisani P, Berrino F, Andreoli C, Barbieri A, Costa A, Marubini E, 1987. Vitamin A and female lung cancer: A case‐control study on plasma and diet. Nutrition and cancer, 10(4): 171-179
33. Pham-Huy LA, He H, Pham-Huy C, 2008. Free radicals, antioxidants in disease and health. International Journal of Biomedical Science: IJBS, 4(2): 89.
34. Pradeep CR, Kuttan G, 2003. Effect of [beta]-carotene on the inhibition of lung metastasis in mice. Phytomedicine, 10(2/3): 159.
35. Pryor WA, 1991. Can vitamin E protect humans against the pathological effects of ozone in smog?. The American Journal of Clinical Nutrition, 53(3): 702-722.
36. Renaud S, De Lorgeril M, Delaye J, Guidollet J, Jacquard F, Mamelle N, Toubol P, 1995. Cretan Mediterranean diet for prevention of coronary heart disease. The American Journal of Clinical Nutrition, 61(6): 1360-1367.
37. Ricciardi V, Portaccio M, Piccolella S, Manti L, Pacifico S, Lepore M, 2017. Study of SH-SY5Y cancer cell response to treatment with polyphenol extracts using FT-IR spectroscopy. Biosensors, 7(4): 57.
38. Ringer TV, De Loof MJ, Winterrowd GE, Francom SF, Gaylor SK, Ryan JA, Hughes GS, 1991. Beta-carotene's effects on serum lipoproteins and immunologic indices in humans. The American Journal of Clinical Nutrition, 53(3): 688-694.
39. Shamberger RJ, 1972. Increase of peroxidation in carcinogenesis. Journal of the National Cancer Institute, 48(5): 1491-1497.
40. Sinnberg T, Noor S, Venturelli S, Berger A, Schuler P, Garbe C, Busch C, 2014. The ROS‐induced cytotoxicity of ascorbate is attenuated by hypoxia and HIF‐1alpha in the NCI 60 cancer cell lines. Journal of Cellular and Molecular Medicine, 18(3): 530-541.
41. Smith MT, Thor H, Hartzell P, Orrenius S, 1982. The measurement of lipid peroxidation in isolated hepatocytes. Biochemical Pharmacology, 31(1): 19-26.
42. Steed MM, Tyagi SC, 2011. Mechanisms of cardiovascular remodeling in hyperhomocysteinemia. Antioxidants & redox signaling, 15(7): 1927-1943.
43. Tartik M, Darendelioglu E, Aykutoglu G, Baydas G, 2016. Turkish propolis supresses MCF-7 cell death induced by homocysteine. Biomedicine & Pharmacotherapy, 82: 704-712.
44. Temel Y, Ayna A, Hamdi Shafeeq I, Ciftci M, 2018. In vitro effects of some antibiotics on glucose-6-phosphate dehydrogenase from rat (Rattus norvegicus) erythrocyte. Drug and chemical toxicology, 1-5.
45. Tyagi N, Sedoris KC, Steed M, Ovechkin AV, Moshal KS, Tyagi SC, 2005. Mechanisms of homocysteine-induced oxidative stress. American Journal of Physiology-Heart and Circulatory Physiology, 289(6): 2649-2656.
46. Van Poppel G, Goldbohm RA, 1995. Epidemiologic evidence for beta-carotene and cancer prevention. The American Journal of Clinical Nutrition, 62(6): 1393-1402.
47. Ziegler RG, 1989. A review of epidemiologic evidence that carotenoids reduce the risk of cancer. The Journal of Nutrition, 119(1): 116-122.