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العنوان
Pharmacological Study on Effect of Resveratrol on Human Colorectal Cancer Cell Lines /
المؤلف
Hafez, Mariam Ahmed Fouad.
هيئة الاعداد
باحث / هبة السيد محمد شرف الدين
مشرف / نادية فؤاد السيد ابوالحسن
مشرف / امانى محمد ابراهيم موسى
مشرف / مروة عوض عبدالمجيد ابراهيم
الموضوع
Pharmacology. Toxicology.
تاريخ النشر
2012.
عدد الصفحات
141 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
علم الأنسجة
تاريخ الإجازة
18/8/2015
مكان الإجازة
جامعة طنطا - كلية الطب - الهستولوجيا
الفهرس
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Abstract

AIM: to examine the antitumor activity of resveratrol in human colorectal cell lines (HCT116 and Caco2) and to explore its mechanism of action assuming that it has calorie restriction effect. METHODS: SRB assay was used for resveratrol cytotoxicity testing. The calorie restriction potential of resveratrol was explored by measuring the following parameters; glucose consumption of cells, citrate synthase, pyruvate kinase and lactate dehydrogenase activities, insulin expression by immunocytochemistry technique, leptin and c-Myc expressions via Western blotting technique. The apoptotic markers like Bcl-2, Bax, caspase 8 and caspase 3 were evaluated via Western blotting technique. Finally, ELISA measurement of VEGF secretion was determined in surrounding incubation media of cells. RESULTS: Untreated control cells of Caco2 cells appeared with significant increase in glycolytic pathway and VEGF secretion with time a behavior which was absent in HCT116 cells. By resveratrol treatment, the proliferation of colon cancer cells was inhibited with IC50 equals 50 and 130 μM for HCT116 and Caco2 respectively. In Caco2 cells only, pyruvate kinase activity was significantly decreased (0.075 U/ mg protein ± 0.01 at 72 h vs 0.13 U/ mg protein ± 0.02 at 48 h at P value < 0.05) and lactate dehydrogenase also decreased significantly by 15.02% and 8.51% after 48 and 72 h respectively. While, decrease in glucose consumption and increase in citrate synthase activity was observed in both cell lines. There was induction of insulin expression. However, there was down regulation in leptin and c- Myc expressions with time. Bax/ Bcl-2 ratio was 3 folds higher in HCT116 cell line than in Caco2. Also, caspase 8 was activated in HCT116 cells and caspase 3 was activated in both cell lines. The content of VEGF in surrounding media was significantly reduced in both cell lines.
CONCLUSION: The aggressive behavior of Caco2 cell line causes to be more resistant to resveratrol cytotoxic and apoptotic effect than HCT116 cell line. The study suggested that resveratrol is promising compound acts by multiple mechanisms, calorie restriction pathway may be one of the driving forces for its anticancer activity.