Salix aegyptiaca L.nin etanolik özütünün akt sinyal yolaği araciliğiyla kolon kanseri üzerinde anti-karsinojenik etkileri.


Tezin Türü: Doktora

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

Tezin Onay Tarihi: 2013

Tezin Dili: İngilizce

Öğrenci: Shabnam Enayat

Danışman: SREEPARNA BANERJEE

Özet:

Salix aegyptiaca has been used for centuries as a medicinal plant for various health disorders. Our previous study demonstrated high contents of phenolics and antioxidants in its bark many of those are famed for their anti-inflammatory properties. Since inflammation frequently accompanies the progress of colorectal cancer, in the current study we showed that the ethanolic extract of bark (EEB) from S.aegyptiaca exerted strong anti-proliferative effects on several cancer cells but not on non-cancerous CCD-18Co cells. Ethyl acetate and water fractions, obtained by solvent-solvent fractionation of EEB showed strong antiproliferative effects comparable to the effect from EEB. Both fractions were applied to tandom mass spectrometry. Catechin, salicin and catechol in Ethyl acetate and salicin in aqueous fractions were the most abundant compounds. Additionally, treatment with the extract induced apoptosis and cell cycle arrest at G1/S, not by DNA damage, but by decreasing phosphorylation and activity of Akt/PKB, stabilizing p53 and upregulating p21. The extract strongly reduced the superoxide anion production in cancer cells but not normal cells. In addition, EEB strongly inhibited anchorage independent growth of colon cancer cell lines HCT-116 and HT-29. Moreover, EEB could inhibit the motility, determined by scratch wound healing and migration through Transwells and adhesion of cancer cells to fibronectin. These in vitro functional changes were accompanied by the downregulation of the EMT markers SNAI1, SNAI2, Twist1, MMP9 and MMP2 and a restoration of E-cadherin expression. We propose that EEB from S.aegyptiaca, with its myriad cancer chemopreventive effects, can be consumed for its health promoting effects.