E vitamini türevli yeni bir molekülün prostat kanseri hücre hattı üzerindeki etkileri.


Tezin Türü: Doktora

Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Edebiyat Fakültesi, Biyolojik Bilimler Bölümü, Türkiye

Tezin Onay Tarihi: 2016

Tezin Dili: İngilizce

Öğrenci: Nuri Ergen

Danışman: FERİDE SEVERCAN

Özet:

Cancer is a complex disease characterized by uncontrolled cell proliferation, invasion and metastasis. It is known that vitamins having high antioxidant capacity, like vitamin A, C and E, play important roles in adjuvant therapy and as cancer protective agents. Vitamin E is a group of fat soluble antioxidant nutrients consisting of tocopherols and tocotrienols. Various research has been performed on the utility of vitamin E derivatives on cancer treatment. Energy metabolism of cells alters during cancer progression due to the increased energy need of cells. Changes in fatty acid, phospholipid and triglyceride amounts in cancer cells were reported in previous studies. Prostate cancer cells, which are regulated by the lipid derivative molecules like androgen have remarkable changes in lipid metabolism. A novel vitamin E derived compound, which has modification on the side chain, was used in this study in order to reveal its roles on cancer progression and cancer lipid metabolism. Based on several experiments performed in this study, it has been concluded that alpha tocopherol derived compound had less toxicity to normal prostate epithelium and compound treatment caused reduction in proliferation and increase in apoptosis of the prostate cancer cell line LNCaP by causing mitochondrial membrane depolarization. Also, cells treated with the novel compound had a remarkable reduction in their motility and migration capacity implying anti metastatic activity and compound treatment led to alterations on lipid metabolism which were detected at both spectroscopic and protein, mRNA levels. Additionally, cells treated with compound show decreased lipid peroxidation as well as increased lipid order that leads to changes in cellular membrane structure. These properties of alpha tocopherol derived compound emphasize the importance of this molecule as a possible therapeutic option in prostate carcinogenesis.