Melatoninin meme kanseri kök hücrelerindeki otofajik etkisininin incelenmesi
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Dosyalar
Tarih
2014
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Selçuk Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Kanser kök hücreleri (KKH) diğer kanserlerde de olduğu gibi, meme kanserinin tanısı, önlenmesi, kan damarı oluşumunu teşvik eden, hücre motilitesini destekleyen ve çeşitli tedavilere direnç gösteren belirli özellikler sergilemektedir. KKH, kemoterapiye oldukça direnç gösteren bir mekanizmaya sahip olmasının yanısıra normal kök hücrelerle benzer bir çok özelliğe sahiptir. KKH ve otofaji arasındaki ilişkinin araştırıldığı birçok çalışmada, büyüme faktörlerinden yoksun tümör hücrelerinde otofajide artış olduğu, hücrelerin ölümden otofaji ile kaçtığı ve hücrelerdeki otofaji inhibe edildiğinde, hücrelerin apoptoz ile öldüğü gözlenmiştir. Otofajinin tümör hücrelerini ölümden koruyan bir mekanizma olduğuna dair hipoteze karşı otofajinin kanser oluşumunu önleyici rolünü gösteren birçok çalışma da bulunmaktadır. Melatonin (5-methoxy-N-acetyltryptamine), epifiz bezinde triptofan aminoasitinden sentezlenmektedir ve farklı dokularda farklı işlevler gösterebilmektedir. Melatoninin anti-kanser özelliği; MCF-7 insan meme kanseri hücrelerinde, p53 ve p21 genleri üzerinden apoptozisi indüklediği, dolayısıyla hücre proliferasyonunu inhibi ettiği bildirilmiştir. Mevcut calışmada, melatonin MCF-7'den izole edilen CD44+/CD24-'lü kök hücre miktarını %35-40 oranında azalttığı (p=0,0106), bunun yanı sıra kontrol hücre grubu olarak kullanılan HEK293'ten izole edilen CD44+/CD24- kök hücre miktarında %20-25 oranında artışa (p=0,0493) sebep olduğu tespit edildi. Kanser kök hücresindeki bu azalmadan sorumlu olabilecek mekanizmalardan biri olan otofaji incelendi. Otofaji belirteci olan LC3-II immünofloresan ve western blot teknikleri ile analiz edildi. Elde ettiğimiz immünofloresan bulguları sonucunda, melatonin uygulanan MCF-7 CD44+/CD24-'lü kök hücrelerinde LC3-II agregasyonu artarken (p=0,0255), HEK293 CD44+/CD24-'lü kök hücrelerde ise LC3-II agregasyonunun azaldığı (p=0,1595) gösterilmiştir. Melatonin uygulanan MCF-7 CD44+/CD24-'lü kök hücrelerde Western blot yöntemi ile incelenen LC3-I'in LC3-II'ye dönüşümü artarken (p=0,0086), HEK293 CD44+/CD24- kök hücrelerde LC3-I'in LC3-II'ye dönüşümünde azalma olduğu tespit edilmiştir (p=0,0089). Literatürdeki veriler ve mevcut calışmadan elde edilen bulgular, melatonin kanser kök hücrelerinde otofaji yolağı üzerinde etkisi olduğu ve bu etkinin kanser kök hücrelerinde bir ölüm mekanizması olan otofajide artışını tetiklediğini göstermektedir. Buna karşın, melatonin HEK293 CD44+/CD24-'lü kök hücrelerinde otofaji yolağını baskılama yönünde etkisinin olduğu gösterildi.
Cancer stem cells (CSC) as well as in other cancers, breast cancer diagnosis, prevention, which stimulates the formation of blood vessels, promote cell motility and exhibits specific properties that are resistant to various treatments. CSC, as well as being a mechanism of resistance to chemotherapy is showing quite a lot of features similar to normal stem cells. CSC and in many studies investigating the relationship between autophagy, the lack of tumor cell growth factor from an increase in autophagy, the cell death of autophagy and how he and the cells of the autophagy is inhibited, it was observed that die by apoptosis of cells. Cancer formation of autophagy in tumor cells, autophagy protects against the hypothesis that the mechanism of death there are many studies showing the inhibitory role. Melatonin (5-methoxy-N-acetyltryptam a) is synthesized from the amino acid tryptophan in the pineal gland and can exhibit different functions in different tissues. Of anti-cancer properties and melatonin; MCF-7 human breast cancer cells by inducing apoptosis via p53 and p21 genes, so it is reported that the inhibition of cell proliferation. In the present study, melatonin in MCF-7 isolated from CD44+/CD24- the amount of stem cells decreases by 35-40% (p = 0.0106), as well as the control group of cells used HEK293 the isolated CD44+/CD24- the amount of stem cells increased by 20-25% (p = 0.0493) was found to be caused. One of the mechanisms that may be responsible for this reduction in cancer stem cells, which were examined autophagy. Autophagy is a marker LC3-II was analyzed by western blot and immunofluorescence techniques. As a result we obtained immunofluorescence findings, melatonin treated MCF-7 CD44+/CD24- stem cells LC3-II aggregation increased (p = 0.0255), HEK293 CD44+/CD24- in stem cells is decreased LC3-II aggregation (p = 0.1595) is shown. Melatonin treated MCF-7 CD44+/CD24- stem cells in Western blot with the examined LC3-I to LC3-II transformation increased (p = 0.0086), HEK293 CD44+/CD24- stem cells LC3-In LC3-II was determined by a reduction in conversion (p = 0.0089). Data and findings from existing studies in the literature on cancer stem cells, melatonin has an effect on autophagy pathway and this is a mechanism of death in active cancer stem cells suggests that triggered the increase in autophagy. However, melatonin HEK293 CD44+/CD24- in the direction of the effect of stem cells that were shown to suppress autophagy pathway.
Cancer stem cells (CSC) as well as in other cancers, breast cancer diagnosis, prevention, which stimulates the formation of blood vessels, promote cell motility and exhibits specific properties that are resistant to various treatments. CSC, as well as being a mechanism of resistance to chemotherapy is showing quite a lot of features similar to normal stem cells. CSC and in many studies investigating the relationship between autophagy, the lack of tumor cell growth factor from an increase in autophagy, the cell death of autophagy and how he and the cells of the autophagy is inhibited, it was observed that die by apoptosis of cells. Cancer formation of autophagy in tumor cells, autophagy protects against the hypothesis that the mechanism of death there are many studies showing the inhibitory role. Melatonin (5-methoxy-N-acetyltryptam a) is synthesized from the amino acid tryptophan in the pineal gland and can exhibit different functions in different tissues. Of anti-cancer properties and melatonin; MCF-7 human breast cancer cells by inducing apoptosis via p53 and p21 genes, so it is reported that the inhibition of cell proliferation. In the present study, melatonin in MCF-7 isolated from CD44+/CD24- the amount of stem cells decreases by 35-40% (p = 0.0106), as well as the control group of cells used HEK293 the isolated CD44+/CD24- the amount of stem cells increased by 20-25% (p = 0.0493) was found to be caused. One of the mechanisms that may be responsible for this reduction in cancer stem cells, which were examined autophagy. Autophagy is a marker LC3-II was analyzed by western blot and immunofluorescence techniques. As a result we obtained immunofluorescence findings, melatonin treated MCF-7 CD44+/CD24- stem cells LC3-II aggregation increased (p = 0.0255), HEK293 CD44+/CD24- in stem cells is decreased LC3-II aggregation (p = 0.1595) is shown. Melatonin treated MCF-7 CD44+/CD24- stem cells in Western blot with the examined LC3-I to LC3-II transformation increased (p = 0.0086), HEK293 CD44+/CD24- stem cells LC3-In LC3-II was determined by a reduction in conversion (p = 0.0089). Data and findings from existing studies in the literature on cancer stem cells, melatonin has an effect on autophagy pathway and this is a mechanism of death in active cancer stem cells suggests that triggered the increase in autophagy. However, melatonin HEK293 CD44+/CD24- in the direction of the effect of stem cells that were shown to suppress autophagy pathway.
Açıklama
Bu araştırma Selçuk Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü tarafından proje numarası: 13202029 ile desteklenmiştir.
Anahtar Kelimeler
Tumor stem cells, Tümör kök hücreleri, Autophagy, Otofaji, Neoplasms, Neoplazmlar, Breast neoplasms, Meme neoplazmları, Melatonin, Melatonin
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Dönmez, H. (2014). Melatoninin meme kanseri kök hücrelerindeki otofajik etkisininin incelenmesi. Selçuk Üniversitesi Yayımlanmış yüksek lisans tezi, Konya.