Melatoninin meme kanseri kök hücrelerindeki otofajik etkisininin incelenmesi


Dr. Öğr. Üyesi HÜSEYİN DÖNMEZ

Tez Türü: Yüksek Lisans

Tezin Yürütüldüğü Kurum: Selçuk Üniversitesi, Tıp Fakültesi / Sağlık Bilimleri, Türkiye

Tez Danışmanı: Yrd. Doç. Dr. Nadir Koçak

Tezin Onay Tarihi: 2014

Tezin Dili: Türkçe

Desteklendiği Program: Diğer

Özet:

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.