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In Vitro Investigation of the Effects of Cape Contribution to Chemotherapeutic Drug Treatment on the Neuroblastoma Cell Line (SH SY- 5Y) on the Inflammatory Process

Year 2022, Volume: 3 Issue: 1, 284 - 297, 07.04.2022

Abstract

Nöroblastom pediatrik grupta yüksek riskli hastalarda çoklu tedavilere cevapsız kalan ve 5 yıllık sağkalım oranı %50’den düşük olan sempatik sinir sistemi tümörüdür. Tedavi protokollerinde evrelerine göre kemoterapi, radyoterapi, cerrahi kullanılsa da bu tedavilerin komplikasyonları ve toksik etkileri de mortaliteyi artıran sebepler arasında bulunmaktadır. Topotekan nöroblastom tedavisinde aktif olarak kullanılmaktadır. Sağ kalım süresini artırıcı etkisi olsa da toksik etkileri nedeni ile kullanımı sınırlanmaktadır. Bu sebeplerle nöroblastom, tedavide yeni yaklaşımlara ve mevcut tedavilerin komplikasyonlarını azaltacak ajanlara ihtiyacı olan bir hastalıktır. CAPE antienflamatuar, immünomodülatör, antioksidan ve antikanser özellikleri bilinen ve özellikle kanser hücrelerini seçici olarak etkilemesi ile tercih edilen doğal bir bileşiktir. Kanser tedavisi sırasında inflamatuar mikroçevrenin düzenlenmesi tedavi planında önem arzetmektedir. Enflamasyon hem pro- hem de anti-tümör özelliklere sahip düzenleyici bir sistemdir. Bu bilgiler doğrultusunda çalışmamızda SHSY-5Y NB hücre hattında Topotekan ve CAPE tedavilerinin enflamatuar sürece etkilerini IL-1α, IL-6, IL-18 ve VEGF antikorları ile apoptotik sürece etkilerini de TUNEL yöntemini kullanarak karşılaştırmayı amaçladık.
Çalışmamızda SH-SY5Y nöroblastom hücre hattı kullanıldı. Hücreler çoğaltıldıktan sonra ICC ve Tunel Boyamaları için ayrı ayrı iki grup oluşturuldu. Her bir grup kendi içinde dörde ayrılarak 1. ve 2. gruplara Topotekan ve CAPE ayrı ayrı, 3. gruba Topotekan ve CAPE birlikte verildi, 4. gruba herhangi bir madde verilmeyerek etken maddelere 24 saat boyunca maruz bırakıldı. Ardından ICC ve TUNEL metodları ile boyama işlemleri yapıldı. Elde edilen bulgularda CAPE+Topotekan uygulanan grupta belirgin olmak üzere CAPE ve Topotekan uygulanan gruplarda IL-1α, IL-6, IL-18 ve VEGF boyanma şiddetleri artmış olarak bulundu. TUNEL boyaması ile yapılan değerlendirmede ise en fazla apoptotik hücre CAPE uygulanan grupta görülmekle beraber Topotekan ve CAPE+Topotekan uygulanan gruplarda da apoptosis artışı saptandı. Çalışmamızın sonuçları SH-SY5Y nöroblastom hücrelerinde CAPE ve Topotekanın inflamasyonu şiddetlendirerek apoptosisi tetiklediğini, CAPE grubunda daha fazla apoptotik hücre görülmesinin Topotekana göre bu hücrelerde daha sitotoksik etkili olduğunu, beraber kullanıldığında ise CAPE’nin Topotekana sinerjistik etkili olduğunu göstermiştir.
Anahtar Kelimeler: Apoptosis, CAPE, İnflamasyon, SHSY-5Y, Topotekan

Supporting Institution

Afyonkarahisar BAP

Project Number

20.GENEL.009.

References

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Nöroblastom Hücre Hattı Üzerinde (SH SY- 5Y) Kemoteröpatik İlaç Tedavisine Cape Katkısının İnflamatuvar Sürece Etkilerinin İn Vitro Araştırılması

Year 2022, Volume: 3 Issue: 1, 284 - 297, 07.04.2022

Abstract

Project Number

20.GENEL.009.

References

  • Referans 1. Pastor ER, Mousa SA. Current management of neuroblastoma and future direction. Critical reviews in oncology/hematology. 2019;138:38-43.
  • Referans2. Peifer M, Hertwig F, Roels F, Dreidax D, Gartlgruber M, Menon R, et al. Telomerase activation by genomic rearrangements in high-risk neuroblastoma. Nature. 2015;526(7575):700-4.
  • Referans3. Jin Z, Lu Y, Wu Y, Che J, Dong X. Development of differentiation modulators and targeted agents for treating neuroblastoma. European Journal of Medicinal Chemistry. 2020:112818.
  • Referans4. Ackermann S, Cartolano M, Hero B, et al. A mechanistic classification of clinical phenotypes in neuroblastoma. Science. 2018;362(6419):1165-70.
  • Referans5. Brodeur GM. Spontaneous regression of neuroblastoma. Cell and tissue research. 2018;372(2):277-86.
  • Referans6. Joshi S. Targeting the tumor microenvironment in neuroblastoma: recent advances and future directions. Cancers. 2020;12(8):2057.
  • Referans7. Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics, 2016. CA: a cancer journal for clinicians. 2016;66(4):271-89.
  • Referans8. Smith V, Foster J. High-risk neuroblastoma treatment review. Children. 2018;5(9):114.
  • Referans9. Tolbert VP, Matthay KK. Neuroblastoma: clinical and biological approach to risk stratification and treatment. Cell and tissue research. 2018;372(2):195-209.
  • Referans10. Geurten C, Geurten M, Hoyoux C, Lebrethon M-C. Endocrine consequences of neuroblastoma treatment in children: 20 years’ experience of a single center. Journal of Pediatric Endocrinology and Metabolism. 2019;32(4):347-54.
  • Referans11. Berthold F, Hero B. Neuroblastoma. Drugs. 2000;59(6):1261-77.
  • Referans12. Koster DA, Palle K, Bot ES, Bjornsti M-A, Dekker NH. Antitumour drugs impede DNA uncoiling by topoisomerase I. Nature. 2007;448(7150):213-7.
  • Referans13. BEKER B. ÇOCUKLUK ÇA⁄ I KANSERLER‹ NDE KEMOTERAP‹.
  • Referans14. Längler A, Christaras A, Abshagen K, Krauth K, Hero B, Berthold F. Topotecan in the treatment of refractory neuroblastoma and other malignant tumors in childhood-a phase-II-study. Klinische Pädiatrie. 2002;214(04):153-6.
  • Referans15. Dobrowolski JW, Vohora S, Sharma K, Shah SA, Naqvi S, Dandiya P. Antibacterial, antifungal, antiamoebic, antiinflammatory and antipyretic studies on propolis bee products. Journal of ethnopharmacology. 1991;35(1):77-82.
  • Referans16. Pascual C, Gonzalez R, Torricella R. Scavenging action of propolis extract against oxygen radicals. Journal of Ethnopharmacology. 1994;41(1-2):9-13.
  • Referans17. Dimov V, Ivanovska N, Bankova V, Popov S. Immunomodulatory action of propolis: IV. prophylactic activity against gram-negative infections and adjuvant effect of the water-soluble derivative. Vaccine. 1992;10(12):817-23.
  • Referans18. Edenharder Rv, Von Petersdorff I, Rauscher R. Antimutagenic effects of flavoniods, chalcones and structurally related compounds on the activity of 2-amino-3-methylinidazo [4, 5-ƒ] quinoline (IQ) and other heterocyclic amine mutagens from cooked food. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 1993;287(2):261-74.
  • Referans19. Krol W, Czuba Z, Scheller S, Gabrys J, Grabiec S, Shani J. Anti-oxidant property of ethanolic extract of propolis (EEP) as evaluated by inhibiting the chemiluminescence oxidation of luminol. Biochemistry International. 1990;21(4):593-7.
  • Referans20. Sud'Ina G, Mirzoeva O, Pushkareva M, Korshunova GA, Sumbatyan N, Varfolomeev S. Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties. FEBS letters. 1993;329(1-2):21-4.
  • Referans21. Beppu K, Nakamura K, Linehan WM, Rapisarda A, Thiele CJ. Topotecan blocks hypoxia-inducible factor-1α and vascular endothelial growth factor expression induced by insulin-like growth factor-I in neuroblastoma cells. Cancer research. 2005;65(11):4775-81.
  • Referans22. Lee Y-J, Kuo H-C, Chu C-Y, Wang C-J, Lin W-C, Tseng T-H. Involvement of tumor suppressor protein p53 and p38 MAPK in caffeic acid phenethyl ester-induced apoptosis of C6 glioma cells. Biochemical pharmacology. 2003;66(12):2281-9.
  • Referans23. Yu H-J, Shin J-A, Yang I-H, et al. Apoptosis induced by caffeic acid phenethyl ester in human oral cancer cell lines: Involvement of Puma and Bax activation. Archives of oral biology. 2017;84:94-9.
  • Referans24. Beauregard A-P, Harquail J, Lassalle-Claux G, Belbraouet M, Jean-Francois J, Touaibia M, et al. CAPE analogs induce growth arrest and apoptosis in breast cancer cells. Molecules. 2015;20(7):12576-89.
  • Referans25. Tseng T-H, Lee Y-J. Evaluation of natural and synthetic compounds from East Asiatic folk medicinal plants on the mediation of cancer. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2006;6(4):347-65.
  • Referans26. Berger N, Ben Bassat H, Klein BY, Laskov R. Cytotoxicity of NF-kappaB inhibitors Bay 11-7085 and caffeic acid phenethyl ester to Ramos and other human B-lymphoma cell lines. Exp Hematol. 2007;35(10):1495-509.
  • Referans27. Chung TW, Moon SK, Chang YC, et al. Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism. Faseb j. 2004;18(14):1670-81.
  • Referans28. Akyol S, Ozturk G, Ginis Z, Armutcu F, Yigitoglu MR, Akyol O. In vivo and in vitro antıneoplastic actions of caffeic acid phenethyl ester (CAPE): therapeutic perspectives. Nutrition and Cancer. 2013;65(4):515-26.
  • Referans29. Dinarello CA. Interleukin-18. Methods. 1999;19(1):121-32.
  • Referans30. Borish LC, Steinke JW. 2. Cytokines and chemokines. J Allergy Clin Immunol. 2003;111(2 Suppl):S460-75.
  • Referans31. Commins SP, Borish L, Steinke JW. Immunologic messenger molecules: cytokines, interferons, and chemokines. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S53-72.
  • Referans32. Salem ML, Attia ZI, Galal SM. Acute inflammation induces immunomodulatory effects on myeloid cells associated with anti-tumor responses in a tumor mouse model. Journal of advanced research. 2016;7(2):243-53.
  • Referans33. Greten FR, Grivennikov SI. Inflammation and cancer: triggers, mechanisms, and consequences. Immunity. 2019;51(1):27-41. Referans34. Carmeliet P. VEGF as a key mediator of angiogenesis in cancer. Oncology. 2005;69 Suppl 3:4-10.
  • Referans35. Zachary I, Gliki G. Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family. Cardiovascular research. 2001;49(3):568-81.
  • Referans36. Weng WC, Lin KH, Wu PY, et al. Calreticulin Regulates VEGF-A in Neuroblastoma Cells. Mol Neurobiol. 2015;52(1):758-70.
  • Referans37. Becker J, Pavlakovic H, Ludewig F, et al. Neuroblastoma progression correlates with downregulation of the lymphangiogenesis inhibitor sVEGFR-2. Clin Cancer Res. 2010;16(5):1431-41.
  • Referans38. Xie H-r, Hu L-s, Li G-y. SH-SY5Y human neuroblastoma cell line: in vitrocell model of dopaminergic neurons in Parkinson's disease. Chinese medical journal. 2010;123(8):1086-92.
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There are 70 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Articles
Authors

Çiğdem Karaca

Hilal Susam Şen 0000-0002-1329-1287

Fatma Fırat 0000-0002-1880-546X

Esra Aslan 0000-0002-3191-4978

Project Number 20.GENEL.009.
Early Pub Date March 31, 2022
Publication Date April 7, 2022
Published in Issue Year 2022 Volume: 3 Issue: 1

Cite

Vancouver Karaca Ç, Susam Şen H, Fırat F, Aslan E. In Vitro Investigation of the Effects of Cape Contribution to Chemotherapeutic Drug Treatment on the Neuroblastoma Cell Line (SH SY- 5Y) on the Inflammatory Process. Exp Appl Med Sci. 2022;3(1):284-97.

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