Akademik Veri Yönetim Sistemi
Tezin Türü: Yüksek Lisans
Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Türkiye
Tezin Onay Tarihi: 2015
Tezin Dili: İngilizce
Öğrenci: Meliha Ülger
Danışman: ORHAN ADALI
Özet:Quercetin has been one of the most studied flavonoids for years because of its widespread effects on various health problems and is known to be a potent anti-carcinogenic compound. One possible mechanism that flavonoids may prevent or treat cancer is by regulation of phase I and phase II enzyme activity. Phase I enzymes are xenobiotic metabolizing cytochrome P450 (CYP) enzymes whose functions are activating or inactivating xenobiotic compounds. CYP1A1 and CYP2E1 enzymes are actively found on cancer cells and modify carcinogenic compounds. Phase II enzymes are responsible from conjugation reactions in the body. GSTP1 and NQO1 enzymes are important representatives of phase II enzymes and their function is elimination of possibly carcinogenic metabolites by reduction and conjugation reactions. This study focused on the effects of quercetin on CYP1A1, CYP2E1, GSTP1 and NQO1 enzymes in human colon carcinoma cell line SW620. In order to study these effects, cells were grown as in 5% CO2 incubator prior to the treatment with quercetin with respect to IC50 value that is determined as 90 µM, and then the effects of quercetin on protein and mRNA expressions are analyzed according to the control groups by Western Blotting and q-RT-PCR, respectively. Quercetin treatment caused 47 % decrease in CYP1A1 protein expression (p<0.01) and 17 % decrease in CYP2E1 protein expression (p<0.01). Furthermore, quercetin treatment caused 85 % decrease in CYP1A1 mRNA expression and 97 % decrease in CYP2E1 mRNA expression with respect to control cells and results are normalized with GAPDH as an internal reference. Moreover, quercetin treatment also caused 35 % decrease in GSTP1 protein expression (p<0.001) and 29 % decrease in NQO1 protein expression (p<0.001). In addition, quercetin treatment caused 75 % decrease in GSTP1 mRNA expression (p<0.05), whereas NQO1 mRNA expression is increased 1.6 fold (p<0.01) after quercetin treatment. In conclusion, the results of this study showed that plant phenolic quercetin can modulate the progression of colon carcinoma by affecting the expression of protein and mRNA of xenobiotic metabolizing phase I and phase II enzymes CYP1A1, CYP2E1, GSTP1 and NQO1.