Effects of 15-lipoxygenase-1 on the angiogenic properties of colorectal cancer cell line SW480

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Tezin Türü: Yüksek Lisans

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

Tezin Onay Tarihi: 2016

Tezin Dili: İngilizce

Öğrenci: CANER YENER

Asıl Danışman (Eş Danışmanlı Tezler İçin): Sreeparna Banerjee

Eş Danışman: İrem Erel Göktepe

Özet:

Colorectal cancer is a disease resulting from the malignant transformation of colon epithelia. As of 2013, it the third leading cause of death among cancer related deaths, in Turkey. Lipoxygenases (LOXs) are a family of fatty acid dioxygenases that convert polyunsaturated fatty acids (PUFAs) to their oxidized form, which are subsequently transformed to bioactive lipid mediators acting in various cell functions. Specifically, 15-Lipoxygenase-1 (15-LOX-1) is a member of the LOX family, oxygenating linoleic acid (LA) preferentially to 13-(S)-HODE as the final product. 15-LOX-1 is known to be important in the resolution of inflammation; the enzyme also has tumor suppressive properties and it can get downregulated in several different cancer types. 15-LOX-1 re-expression in colorectal cancer was shown to decrease metastasis, cell proliferation and invasive capabilities of the cells. We wanted to examine whether re-expression of the enzyme would also lead to a decrease in angiogenic properties. In this context, we assayed the VEGF transcript and secreted protein levels and treated HUVEC cells with conditioned media from SW480 cells expressing 15-LOX-1 . We observed a decrease in both VEGF transcript levels and secreted protein levels in both normoxic and hypoxic conditions. Additionally, HUVECs incubated with conditioned media collected from 15-LOX-1 transfected SW480 cells showed reduced formation of tube-like structures in vitro. In conclusion, 15-LOX-1 re-expression was shown to reduce angiogenic abilities of the colorectal cancer cells.