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العنوان
Biochemical And Molecular Investigations Of Anticarcinogenic Activity Of New Thalidomide Dithiocarbamate Analogs Towards Tumors /
المؤلف
El-Aarag, Bishoy Yousef Abdou.
هيئة الاعداد
باحث / بيشوى يوسف عبده الأعرج
مناقش / سامية عبد السميع شومان
مناقش / أمينة محمد مدحت
مشرف / ماساھارو سينو
الموضوع
Cancer. Cancer - Miscellanea.
تاريخ النشر
2015.
عدد الصفحات
181 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
علم الأورام
الناشر
تاريخ الإجازة
12/2/2015
مكان الإجازة
جامعة المنوفية - كلية الطب - الكيمياء
الفهرس
Only 14 pages are availabe for public view

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Abstract

Inhibition of angiogenesis is currently perceived as a promising strategy in the treatment of cancer. The anti-angiogenicity of thalidomide has inspired a second wave of research on this teratogenic drug. The present study aimed to investigate the antiproliferative and anti-angiogenic activities of two thalidomide dithiocarbamate analogs on human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 human breast cancer cell lines. Their action on the expression levels of IL-6, IL-8, and TNF-α was also assessed. Furthermore, the antiangiogenic potential of the two analogs was evaluated through VEGF165, MMP-2, wound healing, migration, tube formation, and nitric oxide (NO) assays. Results stated that the proliferation of HUVECs and MDA-MB-231 cells was not significantly affected by thalidomide at 6.25–100 μM. Thalidomide failed to block angiogenesis at similar concentrations. In contrast, thalidomide dithiocarbamate analogs exhibited significant anti-proliferative action on HUVECs and MDA-MB-231 cells without causing cytotoxicity and also showed powerful anti-angiogenicity in wound healing, migration, tube formation, and NO assays. Thalidomide analogs 1 and 2 demonstrated more potent activity to suppress expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 than thalidomide. Analog 1 consistently, showed the highest potency and efficacy in all the assays. Taken together, our results support further evaluation of novel thalidomide analogs as anti-tumor and anti-angiogenic agents.