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Beta-Karoten, Alfa-Tokoferol ve Askorbik Asidin PC-3 Prostat Kanser Hücrelerine Apoptotik Etkileri

Year 2020, Volume: 48 Issue: 3, 211 - 218, 15.06.2020
https://doi.org/10.15671/hjbc.519212

Abstract

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.

References

  • 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 low-density 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 follow-up 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 proliferator-activated 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.

APOPTOTIC EFFECTS OF BETA-CAROTENE, ALPHA-TOCOPHEROL AND ASCORBIC ACID ON PC-3 PROSTATE CANCER CELLS

Year 2020, Volume: 48 Issue: 3, 211 - 218, 15.06.2020
https://doi.org/10.15671/hjbc.519212

Abstract

Prostate
cancer (PC) is one of the the most commonly diagnosed cancer type being the
second major reason of cancer-associated death in male particularly over the
age of 50. Accumulating scientific evidences suggest the role oxidative stress
and Reactive oxygen species (ROS) in prostate cancer. ROS are produced by
carcinogenic molecules, infection, toxic compounds all of which can contribute
to disturbed homeostasis and genetic mutation. Antioxidants can decrease the
negative effects of ROS in vitro. The vitamins C (Ascorbic acid, Asc), A (beta
carotenoids and retinoids, β-Crt) and E (alpha tocopherol, α-Toc) play
important role in inhibiting oxidation and reducing the concentration of free
radicals in the body. The aim of this study was to determine the anticancer
effect of α-Toc, β-Crt and Asc on PC-3 prostate cancer cells in vitro. This was
carried out by cell proliferation, ROS and Lipid Peroxidation assay, caspase-3
and propidium iodide staining experiments. The findings suggest that these agents
behave as prooxidant by lowering cell viability and increasing the production
of ROS and LPO in prostate cancer. These oxidants induce apoptosis as supported
by propidium iodide and caspase-3 staining.

References

  • 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 low-density 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 follow-up 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 proliferator-activated 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.
There are 27 citations in total.

Details

Primary Language English
Subjects Engineering
Journal Section Articles
Authors

Adnan Ayna 0000-0001-6801-6242

Publication Date June 15, 2020
Acceptance Date July 11, 2019
Published in Issue Year 2020 Volume: 48 Issue: 3

Cite

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. https://doi.org/10.15671/hjbc.519212
AMA Ayna A. APOPTOTIC EFFECTS OF BETA-CAROTENE, ALPHA-TOCOPHEROL AND ASCORBIC ACID ON PC-3 PROSTATE CANCER CELLS. HJBC. June 2020;48(3):211-218. doi: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 (June 2020): 211-18. https://doi.org/10.15671/hjbc.519212.
EndNote Ayna A (June 1, 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.
IEEE A. Ayna, “APOPTOTIC EFFECTS OF BETA-CAROTENE, ALPHA-TOCOPHEROL AND ASCORBIC ACID ON PC-3 PROSTATE CANCER CELLS”, HJBC, vol. 48, no. 3, pp. 211–218, 2020, doi: 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 (June 2020), 211-218. https://doi.org/10.15671/hjbc.519212.
JAMA Ayna A. APOPTOTIC EFFECTS OF BETA-CAROTENE, ALPHA-TOCOPHEROL AND ASCORBIC ACID ON PC-3 PROSTATE CANCER CELLS. HJBC. 2020;48:211–218.
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, pp. 211-8, doi:10.15671/hjbc.519212.
Vancouver Ayna A. APOPTOTIC EFFECTS OF BETA-CAROTENE, ALPHA-TOCOPHEROL AND ASCORBIC ACID ON PC-3 PROSTATE CANCER CELLS. HJBC. 2020;48(3):211-8.

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