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The Investigastion of Apoptosis Activation and Cyotoxicity of Melatonin in MCF-7 Cell Culture Through Polimerase Chain Reaction (PCR), MTT Cell Viability Assay and Immunocytochemical Methods

Yıl 2024, Cilt: 10 Sayı: 2, 265 - 275, 01.05.2024
https://doi.org/10.53394/akd.1249740

Öz

Objective: Breast cancer, one of the most common cancer types in the world and in Turkey, ranks first among cancer-related deaths. For this reason, new researches are carried out for the treatment of this disease. We aimed to investigate the relationship of melatonin, a powerful antioxidant, with cancer and its contribution to the solution of cancer.
Methods: In our study, melatonin concentrations in the range of 10 nM–100,000 nM were applied to the MCF-7 cell line to determine the cytotoxic doses and IC50 value of melatonin. After melatonin application, cell viability was determined by MTT analysis and effective doses for melatonin were determined. MCF-7 cells were incubated for 24 hours with 5 concentrations (10, 100, 1000, 10,000 and 100,000 nM) doses of melatonin. Melatonin cytotoxicity, TAS, TOS, apoptotic activity (Bax and p53 immunpositivity) and p53 gene expression levels were examined in all groups.
Results: At the end of the 24-hour incubation, it was determined that melatonin administered to MCF-7 cells inhibited cell proliferation and had a cytotoxic effect, increasing p53 gene expression and Bax protein synthesis. It was determined that Bax and p53 immunopositivity increased in immunocytochemical staining. In addition, melatonin treatment increased TAS and decreased TOS.
Conclusion: These effects show that melatonin induces apoptosis activation due to the increase in p53 gene expression and Bax protein, and thus may be an adjunctive agent that can be used in cancer treatment.

Proje Numarası

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Kaynakça

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Melatoninin MCF-7 Hücre Kültüründeki Apoptoz Aktivasyonunun ve Sitotoksisitesinin Polimeraz Zincir Reaksiyonu (PCR), MTT Hücre Canlılık Testi ve İmmunsitokimya Yöntemleriyle Araştırılması

Yıl 2024, Cilt: 10 Sayı: 2, 265 - 275, 01.05.2024
https://doi.org/10.53394/akd.1249740

Öz

Amaç: Dünyada ve Türkiye'de en sık görülen kanser türlerinden biri olan meme kanseri, kanser nedenli ölüm oranları arasında ilk sıralarda yer almaktadır. Bu nedenle bu hastalığın tedavisine yönelik yeni araştırmalar yapılmaktadır. Biz de güçlü bir antioksidan olan melatoninin kanserle ilişkisini ve kanser hastalığının çözümüne katkısını araştırmayı amaçladık.
Yöntemler: Çalışmamızda melatoninin sitotoksik dozlarını ve IC50 değerini belirleyebilmek için MCF-7 hücre hattına 10 nM–100.000 nM aralığında melatonin konsantrasyonları uygulandı. Melatonin uygulamasının ardından MTT analizi ile hücre canlılığı tespiti yapıldı ve melatonin için etkin dozlar belirlendi. MCF-7 hücreleri, 5 konsantrasyon (10, 100, 1000, 10.000 ve 100.000 nM) melatonin dozu ile 24 saat inkübasyon işlemine tabi tutuldu. Tüm gruplarda melatonin sitotoksisitesi, TAS, TOS, apoptotik aktivite (Bax ve p53 immünpozitifliği) ve p53 geninin ekspresyon düzeyleri incelendi.
Bulgular: 24 saatlik inkübasyon sonunda MCF-7 hücrelerine uygulanan melatoninin hücre proliferasyonunu inhibe ederek sitotoksik etki yaptığı, p53 gen ekspresyonunu ve Bax protein sentezini artırdığı tespit edildi. İmmünsitokimyasal boyamada Bax ve p53 immünpozitifliğinin arttığı belirlendi. Ayrıca melatonin tedavisi TAS'ı artırıp TOS'u azalttı.
Sonuç: Bu etkiler, melatoninin p53 gen ekspresyonu ve Bax proteinindeki artışa bağlı olarak apoptoz aktivasyonunu indüklediğini ve dolayısıyla kanser tedavisinde kullanılabilecek yardımcı bir ajan olabileceğini göstermektedir.

Destekleyen Kurum

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Proje Numarası

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Teşekkür

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Kaynakça

  • 1- Kutlu R, Demirbaş N, Börüban MC, Güler T. Sigara içmeye atfedilebilen kanser türleri ve sosyodemografik özellikleri. Turk Onkol Derg 2014; 29(3): 81-8.
  • 2- Yokuş B, Çakır DÜ. Kanser biyokimyası. Dicle Univ Ver Fak Derg 2012; 1: 7-18.
  • 3- Alıcı S, İzmirli M, Doğan E. Yüzüncü Yıl Üniversitesi Tıp Fakültesi Tıbbi Onkoloji Bilim Dalı’na başvuran kanser hastalarının epidemiyolojik değerlendirilmesi. Türk Onkol Derg 2006; 21:87-97.
  • 4- The Global Cancer Observatory (GCO). https://gco.iarc.fr/today/data/factsheets/cancers/20-Breast-fact-sheet.pdf (Erişim tarihi: 20.05.2022)
  • 5- Yazıcı O, Özdemir N. Meme kanserinde epidemiyolojik veriler, risk faktörleri, risk azaltıcı yaklaşımlar. T Klin Tıbbi Onkoloji-Özel Konular 2018; 11(1): 1-7.
  • 6- Sofi MS, Sateesh MK, Bashir M, Ganie MA, Nabi S. Chemopreventive and anti-breast cancer activity of compounds isolated from leaves of Abrus precatorius L. 3 Biotech 2018; 8(8): 371.
  • 7- Misra R, Acharya S, Sahoo SK. Cancer nanotechnology: application of nanotechnology in cancer therapy. Drug Discov Today 2010; 15(19-20): 842-50.
  • 8- Şimşek F, Sevinç İ, Müftüoğlu S, Özbilgin K, Vatansever S, Tuğlu İ. Meme kanseri hücre hatlarında propranolol ve paklitakselin anjiyogenez üzerine etkisi. Cukurova Med J 2019; 44(1): 144-53.
  • 9- Karaman A. Mide kanserinde p53 tümör supresör geninin rolü. Turkiye Klinikleri J Med Sci 2003; 23: 67-73.
  • 10- Özgür MA, Şamlı H, Özgöz A, Solak M, Dilek H. Meme karsinomlarında polimeraz zincir reaksiyonu ve enzim kesimi ile p53 gen mutasyonlarının araştırılması ve dokuda immunohistokimyasal olarak p53 proteininin gösterilmesi. Kocatepe Tıp Derg 2006; 7(1):17-22.
  • 11- Yılmaz E, Altunok V. Kanser ve p53 geni. AVKAE Derg 2011; 1: 19-23.
  • 12- Coşkun G, Özgür H. Apoptoz ve nekrozun moleküler mekanizması. Ars Kay Tar Derg 2011; 20: 145-58.
  • 13- Elmore S. Apoptosis: A review of programmed cell death. Toxıcol Pathol 2007; 35: 495-16.
  • 14- Yerlikaya A, Dokudur H. Protein yıkımının önemi. Uludağ Üniv Tıp Fak Derg 2009; 35: 93-9.
  • 15- Altunkaynak BZ, Özbek E. Programlanmış hücre ölümü: Apoptoz nedir? Tıp Arast Derg 2008; 6: 93-104.
  • 16- Bircan S, Çandır Ö, Kapucuoğlu N, Başpınar Ş. p53, BCL-2, Bax expression in basal cell carcinomas and nontumoral surrounding skin. Turk J Path 2005; 21(3-4): 044-048.
  • 17- Ravindra T, Lakshmi NK, Ahuja YR. Melatonin in pathogenesis and therapy of cancer. IJMS 2006; 60: 523-35.
  • 18- Lissoni P, Rovelli F, Malugani F, Bucovec R, Conti A, Maestroni GJ. Anti-angiogenic activity of melatonin in advanced cancer patients. Neuroendocrınol Lett 2001; 22: 45-7.
  • 19- Fernández R, Güézmes A, Sánchez-Barceló EJ. Influence of melatonin on invasive and metastatic properties of MCF-7 human breast cancer cells. Cancer Res 1998; 58: 4383-90.
  • 20- Cos S, González A, Martínez-Campa C, Mediavilla MD, Alonso- González C, Sánchez-Barceló EJ. Estrogen-signaling pathway: A link between breast cancer and melatonin oncostatic actions. Cancer Detect Prev 2006; 30: 118-28.
  • 21- Cos S, Sánchez-Barceló EJ. Melatonin and mammary pathological growth. Front Neuroendocrin 2000; 21: 133-70.
  • 22- Sánchez-Barceló EJ, Cos S, Fernández R, Mediavilla MD. Melatonin and mammary cancer: a short review. Endocr-Relat Cancer 2003; 10: 153-9.
  • 23- Karabekir G, Demircan G, Özdaş Ş. Resveratrolün MCF-7 hücre soyunda apoptotik etkinin araştırılması. FNG & Bilim Tıp Dergisi 2017; 3(1): 27-34.
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  • 52- Cos S, Blask DE, Lemus-Wilson A, Hill AB. Effects of melatonin on the cell cycle kinetics and "estrogen-rescue" of MCF-7 human breast cancer cells in culture. J Pineal Res 1991; 10: 36-42.
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  • 54- Karbownik M, Lewinski A, Reiter RJ. Anticarcinogenic actions of melatonin which involve antioxidative processes: comparison with other antioxidants. Int J Biochem Cell Biol 2001; 33: 735-53.
  • 55- Matѐs JM. Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology. Toxicology 2000; 153: 83-104.
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  • 58- Reiter RJ, Tan DX, Qi W, Manchester LC, Karbownik M, Calvo JR. Pharmacology and physiology of melatonin in the reduction of oxidative stress in vivo. Biol Signals Recept 2000; 9: 160-71.
  • 59- Albarrán MT, López-Burillo S, Pablos MI, Reiter RJ, Agapito MT. Endogenous rhythms of melatonin, total antioxidant status and superoxide dismutase activity in several tissues of chick and their inhibition by light. J Pineal Res 2001; 30: 227-33.
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  • 79- Hilde E.van Gijssel, Rob P.M.van Gijlswijk, Richard R.de Haas, C Stark, Mulder GJ, Meerman JHN. Immunohistochemical visualization of wild-type p53 protein in paraffin-embedded rat liver using tyramide amplification: Zonal hepatic distribution of p53 protein after N-hydroxy-2-acetylaminofluorene administration. Carcinogenesis 1998; 19: 219-22.
  • 80- Ogawara Y, Kishishita S, Obata T, Isazawa Y, Suzuki T, Tanaka K, Masuyama N, Gotoh Y. Akt enhances Mdm2-mediated ubiquitination and degradation of p53. J Biol Chem 2002; 277: 21843-50.
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  • 83- Leja-Szpak A, Jaworek J, Pierzchalski P, Reiter RJ. Melatonin induces pro-apoptotic signaling pathway in human pancreatic carcinoma cells (PANC-1). J Pineal Res 2010; 49: 248-55.
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Toplam 86 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Klinik Tıp Bilimleri
Bölüm Araştırma Makalesi
Yazarlar

Semin Gedikli 0000-0001-8238-7226

Elvan Şahin 0000-0001-8585-9903

Ahmet Özbek 0000-0001-8938-6533

Abdulgani Tatar 0000-0001-7273-1679

Adem Kara 0000-0002-5766-6116

Ahmet Hacımüftüoğlu 0000-0002-9658-3313

Proje Numarası -
Erken Görünüm Tarihi 10 Mayıs 2024
Yayımlanma Tarihi 1 Mayıs 2024
Gönderilme Tarihi 10 Şubat 2023
Yayımlandığı Sayı Yıl 2024 Cilt: 10 Sayı: 2

Kaynak Göster

APA Gedikli, S., Şahin, E., Özbek, A., Tatar, A., vd. (2024). Melatoninin MCF-7 Hücre Kültüründeki Apoptoz Aktivasyonunun ve Sitotoksisitesinin Polimeraz Zincir Reaksiyonu (PCR), MTT Hücre Canlılık Testi ve İmmunsitokimya Yöntemleriyle Araştırılması. Akdeniz Tıp Dergisi, 10(2), 265-275. https://doi.org/10.53394/akd.1249740