Apoptotic Effects of Beta-Carotene, Alpha-Tocopherol and Ascorbic Acid on PC-3 Prostate Cancer Cells
Yıl: 2020 Cilt: 48 Sayı: 3 Sayfa Aralığı: 211 - 218 Metin Dili: İngilizce DOI: 10.15671/hjbc.519212 İndeks Tarihi: 29-06-2021
Apoptotic Effects of Beta-Carotene, Alpha-Tocopherol and Ascorbic Acid on PC-3 Prostate Cancer Cells
Öz: Prostate cancer (PC) is one of the most commonly diagnosed cancer types being the second major reason of cancerassociateddeath in male particularly over the age of 50. Accumulating scientific evidences suggest the role oxidativestress and reactive oxygen species (ROS) in prostate cancer. A variety of factors including carcinogenic molecules, infectiousdiseases and toxic compounds can induce ROS production which turns into a strong contribution to the disturbedhomeostasis and genetic mutation. Antioxidants can decrease the negative effects of ROS in vitro. Vitamin C (Ascorbicacid, Asc), vitamin A (beta carotenoids and retinoids, β-Crt) and vitamin E (alpha tocopherol, α-Toc) play an important rolein inhibition of oxidative stress and diminishing of free radicals in the body. The aim of this study was to determine theanticancer effect of α-Toc, β-Crt and Asc on PC-3 prostate cancer cells in vitro. This was carried out by cell proliferation, ROSand Lipid Peroxidation assay, caspase-3 and propidium iodide staining experiments. The findings suggest that these agentsbehave as prooxidant by lowering cell viability and increasing the production of ROS and LPO in prostate cancer. Theseoxidants induce apoptosis as supported by caspase-3 (the enzyme playing key role in programmed cell death) staining bydisplaying a marked increase in the expression level of caspase-3 enzyme.
Anahtar Kelime: Beta-Karoten, Alfa-Tokoferol ve Askorbik Asidin PC-3 Prostat Kanser Hücrelerine Apoptotik Etkileri
Öz: Prostat kanseri (PC), özellikle 50 yaşın üzerindeki erkeklerde kansere bağlı ölümlerin ikinci büyük nedeni olan ve en yaygın olarak teşhis edilen kanser tiplerinden biridir. Bilimsel çalışmalar oksidatif stres ve Reaktif oksijen türlerinin (ROS) prostat kanseri üzerindeki rolünü göstermektedir. ROS, kanserojen moleküller, enfeksiyon, toksi bileşikler gibi homeostaza ve genetik mutasyona neden olabilecek bileşikler tarafından üretilir. Antioksidanlar, ROS’un olumsuz etkilerini in vitro olarak azaltabilir. C vitamini (Askorbik asit, Asc), A vitamini (beta karotenoidler ve retinoidler, β-Crt) ve E vitamini (alfa tokoferol, α-Toc) oksidasyonun önlenmesinde ve vücuttaki serbest radikallerin konsantrasyonunun azaltılmasında önemli rol oynar. Bu çalışmanın amacı, α-Toc, β-Crt ve Asc’nin PC-3 prostat kanseri hücreleri üzerindeki in vitro antikanser etkisini belirlemektir. Bu amaç, hücre çoğalması, ROS ve Lipid Peroksidasyon deneyi, kaspaz-3 ve propidium iyodür boyama deneyleri ile gerçekleştirildi. Bulgular, bu ajanların, prostat kanseri hücrelerinde hücre canlılığını azaltarak ve ROS ve LPO üretimini artırarak proksidan olarak davrandığını göstermektedir. Bu oksidanlar kaspaz-3 (programlı hücre ölümünde rol alan önemli bir enzim) boyamasıyla desteklendiği üzere apoptozu kaspaz-3 enziminin ekspresyonunu artırarak indüklemiştir.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- 1. K. Turkekul, R.D. Colpan, T. Baykul, M.D. Ozdemir, S. Erdogan, Esculetin inhibits the survival of human prostate cancer cells by inducing apoptosis and arresting the cell cycle, J. Cancer Prev., 23 (2018) 10-17.
- 2. A. Chomyn, G. Attardi, MtDNA mutations in aging and apoptosis, Biochem. Biophys. Res. Commun., 304(2003), 519-529.
- 3. G.D. Dakubo, R.L. Parr, L.C. Costello, R.B. Franklin, R.E. Thayer, Altered metabolism and mitochondrial genome in prostate cancer. J. Clin. Pathol., 59 (2006) 10-16.
- 4. N. Khurana, S. Sikka, Targeting crosstalk between Nrf-2, NF-κB and androgen receptor signaling in prostate cancer Cancers, 10 (2018) 352.
- 5. G. Barrera, Oxidative stress and lipid peroxidation products in cancer progression and therapy, ISRN Oncol., 2012 (2012), 1-21.
- 6. R.K. Khurana, A. Jain, A. Jain, T. Sharma, B. Singh, P. Kesharwani, Administration of antioxidants in cancer: debate of the decade, Drug Discov. Today, 23 (2018) 763- 770
- 7. A.A. de Carvalho Melo-Cavalcante, L. da Rocha Sousa, M.V.O.B. Alencar, J.V. de Oliveira Santos, A.M. oliveira da Mata, M.F.C. Paz, J. C.R. Gonçalves, Retinol palmitate and ascorbic acid: Role in oncological prevention and therapy, Biomed. Pharmacother., 109 (2019) 1394-1405.
- 8. C. Sato, S. Kaneko, A. Sato, N. Virgona, K. Namiki, T. Yano, Combination Effect of δ-Tocotrienol and γ-Tocopherol on Prostate Cancer Cell Growth. J. Nutr. Sci. Vitaminol., 63 (2017) 349-354.
- 9. S.B. Nimse, D. Pal, Free radicals, natural antioxidants, and their reaction mechanisms. Rsc Adv., 5 (2015) 27986-28006.
- 10. P.K. Witting, J.M. Upston, R. Stocker, Role of α-tocopheroxyl radical in the initiation of lipid peroxidation in human lowdensity lipoprotein exposed to horse radish peroxidase, Biochem., 36 (1997) 1251-1258.
- 11. P. Morlière, L.K, Patterson, C.M. Santos, A.M. Silva, J.C. Mazière, P. Filipe, R. Santus, The dependence of α-tocopheroxyl radical reduction by hydroxy-2, 3-diarylxanthones on structure and micro-environment, Org. Biomol. Chem., 10 (2012) 2068-2076.
- 12. R. Stocker, V.W. Bowry, B. Frei, Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol, Proc. Natl. Acad. Sci. U.S.A., 88 (1991) 1646-1650.
- 13. E. Niki, Role of vitamin E as a lipid-soluble peroxyl radical scavenger: in vitro and in vivo evidence, Free. Radic. Biol. Med., 66 (2014) 3-12.
- 14. E. Niki, Action of ascorbic acid as a scavenger of active and stable oxygen radicals, Am. J. Clin. Nutr., 54 (1991) 1119- 1124.
- 15. K.L. Retsky, M.W. Freeman, B. Frei, Ascorbic acid oxidation product (s) protect human low density lipoprotein against atherogenic modification. Anti-rather than prooxidant activity of vitamin C in the presence of transition metal ions, J. Biol. Chem., 268 (1993) 1304-1309.
- 16. C.W. Oh, M. Li, E.H, Kim, J.S. Park, J.C. Lee, S.W. Ham, Antioxidant and radical scavenging activities of ascorbic acid derivatives conjugated with organogermanium, Bull. Korean Chem. Soc., 31 (2010) 3513-3514.
- 17. J.A. Satia, A. Littman, C.G. Slatore, J.A. Galanko, E. White, Long-term use of β-carotene, retinol, lycopene, and lutein supplements and lung cancer risk: Results from the vitamins and lifestyle (VITAL) study, Am. J. Epidemiol., 169 (2009) 815-828.
- 18. M.T. Smith, H. Thor, P. Hartzell, S. Orrenius, The measurement of lipid peroxidation in isolated hepatocytes, Biochem. Pharmacol., 1 (1982) 19-26.
- 19. M. Tartik, E. Darendelioglu, G. Aykutoglu, G. Baydas, Turkish propolis supresses MCF-7 cell death induced by homocysteine, Biomed. Pharmacother., 82 (2016) 704-712.
- 20. B. Poljsak, D. Šuput, I. Milisav, Achieving the balance between ROS and antioxidants: when to use the synthetic antioxidants, Oxid. Med. Cell. Longev., 2013 (2013).
- 21. F. Hecht, C.F. Pessoa, L.B. Gentile, D. Rosenthal, D.P. Carvalho, R.S. Fortunato, The role of oxidative stress on breast cancer development and therapy, Tumor Biol., 37 (2016) 4281-4291.
- 22. G.E. Goodman, M.D. Thornquist, J. Balmes, M.R. Cullen, F.L. Meyskens Jr, G.S. Omenn, J.H. Williams Jr, The Beta- Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year followup after stopping β-carotene and retinol supplements, J. Natl. Cancer Inst., 96 (2004) 1743-1750.
- 23. W.G. Christen, J.M. Gaziano, C.H. Hennekens, PHYSICIANS, F. T. S. C. O., & STUDY II, H. E. A. L. T. H., Design of Physicians’ Health Study II—a randomized trial of beta-carotene, vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular disease, and eye disease, and review of results of completed trials, Ann. Epidemiol., 10 (2000) 125- 134.
- 24. E.A. Klein, I.M. Thompson, C.M. Tangen, J.J. Crowley, M.S. Lucia, P.J. Goodman, D.D. Karp, Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT), JAMA, 306 (2011) 1549-1556.
- 25. Y. Cui, Z. Lu, L. Bai, Z. Shi, W.E. Zhao, B. Zhao, β-Carotene induces apoptosis and up-regulates peroxisome proliferatoractivated receptor γ expression and reactive oxygen species production in MCF-7 cancer cells, Eur. J. Cancer, 43 (2007) 2590-2601.
- 26. V. Nikoletopoulou, M. Markaki, K. Palikaras, N. Tavernarakis, Crosstalk between apoptosis, necrosis and autophagy, Biochim. Biophys. Acta- Mol. Cell Res., 1833 (2013) 3448- 3459
- 27. J.J. Stevens, B. Graham, E. Dugo, B. Berhaneselassie-Sumner, K. Ndebele, P.B. Tchounwou, Arsenic trioxide induces apoptosis via specific signaling pathways in HT-29 colon cancer cells, J. Cancer Sci. Ther., 9 (2017) 298.
| APA | AYNA A (2020). Apoptotic Effects of Beta-Carotene, Alpha-Tocopherol and Ascorbic Acid on PC-3 Prostate Cancer Cells. , 211 - 218. 10.15671/hjbc.519212 |
| Chicago | AYNA ADNAN Apoptotic Effects of Beta-Carotene, Alpha-Tocopherol and Ascorbic Acid on PC-3 Prostate Cancer Cells. (2020): 211 - 218. 10.15671/hjbc.519212 |
| MLA | AYNA ADNAN Apoptotic Effects of Beta-Carotene, Alpha-Tocopherol and Ascorbic Acid on PC-3 Prostate Cancer Cells. , 2020, ss.211 - 218. 10.15671/hjbc.519212 |
| AMA | AYNA A Apoptotic Effects of Beta-Carotene, Alpha-Tocopherol and Ascorbic Acid on PC-3 Prostate Cancer Cells. . 2020; 211 - 218. 10.15671/hjbc.519212 |
| Vancouver | AYNA A Apoptotic Effects of Beta-Carotene, Alpha-Tocopherol and Ascorbic Acid on PC-3 Prostate Cancer Cells. . 2020; 211 - 218. 10.15671/hjbc.519212 |
| IEEE | AYNA A "Apoptotic Effects of Beta-Carotene, Alpha-Tocopherol and Ascorbic Acid on PC-3 Prostate Cancer Cells." , ss.211 - 218, 2020. 10.15671/hjbc.519212 |
| ISNAD | AYNA, ADNAN. "Apoptotic Effects of Beta-Carotene, Alpha-Tocopherol and Ascorbic Acid on PC-3 Prostate Cancer Cells". (2020), 211-218. https://doi.org/10.15671/hjbc.519212 |
| APA | AYNA A (2020). Apoptotic Effects of Beta-Carotene, Alpha-Tocopherol and Ascorbic Acid on PC-3 Prostate Cancer Cells. Hacettepe Journal of Biology and Chemistry, 48(3), 211 - 218. 10.15671/hjbc.519212 |
| Chicago | AYNA ADNAN Apoptotic Effects of Beta-Carotene, Alpha-Tocopherol and Ascorbic Acid on PC-3 Prostate Cancer Cells. Hacettepe Journal of Biology and Chemistry 48, no.3 (2020): 211 - 218. 10.15671/hjbc.519212 |
| MLA | AYNA ADNAN Apoptotic Effects of Beta-Carotene, Alpha-Tocopherol and Ascorbic Acid on PC-3 Prostate Cancer Cells. Hacettepe Journal of Biology and Chemistry, vol.48, no.3, 2020, ss.211 - 218. 10.15671/hjbc.519212 |
| AMA | AYNA A Apoptotic Effects of Beta-Carotene, Alpha-Tocopherol and Ascorbic Acid on PC-3 Prostate Cancer Cells. Hacettepe Journal of Biology and Chemistry. 2020; 48(3): 211 - 218. 10.15671/hjbc.519212 |
| Vancouver | AYNA A Apoptotic Effects of Beta-Carotene, Alpha-Tocopherol and Ascorbic Acid on PC-3 Prostate Cancer Cells. Hacettepe Journal of Biology and Chemistry. 2020; 48(3): 211 - 218. 10.15671/hjbc.519212 |
| IEEE | AYNA A "Apoptotic Effects of Beta-Carotene, Alpha-Tocopherol and Ascorbic Acid on PC-3 Prostate Cancer Cells." Hacettepe Journal of Biology and Chemistry, 48, ss.211 - 218, 2020. 10.15671/hjbc.519212 |
| ISNAD | AYNA, ADNAN. "Apoptotic Effects of Beta-Carotene, Alpha-Tocopherol and Ascorbic Acid on PC-3 Prostate Cancer Cells". Hacettepe Journal of Biology and Chemistry 48/3 (2020), 211-218. https://doi.org/10.15671/hjbc.519212 |
