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العنوان
Analyzing the apoptotic pathways in cell lines treated with some pure natural compounds /
المؤلف
Ramadan,Doaa Taha.
هيئة الاعداد
باحث / Doaa Taha Ramadan
مشرف / Wael M. El-Sayed
مشرف / Shaymaa M. Yahya
مشرف / Mohamed A. M. Ali
تاريخ النشر
2018
عدد الصفحات
125p.;
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
علم الحيوان والطب البيطري
تاريخ الإجازة
1/1/2018
مكان الإجازة
جامعة عين شمس - كلية العلوم - علم الحيوان
الفهرس
Only 14 pages are availabe for public view

from 125

from 125

Abstract

Cancer is the second leading cause of death after cardiovascular disorder and is the leading one in old age. free radicals known as reactive oxygen species (ROS) such as the superoxide radical (•O2 ), hydroxyl radical (•OH) and hydrogen peroxide (H2O2), are constantly generated in our bodies from contact with foreign chemicals. Normally, the ROS generated in human body are cleared by the intrinsic or extrinsic antioxidants in the body. However, owing to ROS overproduction or insufficient antioxidant defense, this balance is disturbed favoring the ROS increase that end up in oxidative stress. Although the body has effective defense mechanisms that protect it against oxidative stress, there is a need to provide the body with a constant supply of antioxidants through dietary supplements. The aim of the present study is to critically discuss the antioxidant, antiproliferative and antimutagenic activities of pure flavonoids from dietary plants. This study found that they possess multiple biological actions and may be helpful in the prevention and therapy of cancer. The prooxidative and antioxidative properties of investigated phenolic compounds, amygdalin, naringenin, and ellagic acid was studied. They represent plant secondary metabolites that belong to glycosides, flavonoids, and polyphenols, respectively.
The study investigated antioxidant molecules and free radical scavenger based on their ability to chelate metal ions, reduce ferric to ion, scavenge non-biological stable free radical (DPPH•) and scavenge biologically important oxidants such as H2O2 and •OH. Treatment of HCT-116, HepG2 and MCF-7 cell lines for 48 hours, all examined pure compounds showed a cytotoxic activity. By comparing the results of activities of examined compounds, it can be concluded that ellagic acid showed the highest cytotoxic activity especially on MCF-7 human breast cell lines. Amygdalin which is a glycoside did not exhibit cytotoxic effect except at high concentration (10 mg/ml) especially on HCT-116 and MCF-7cells, it induced a weak inhibition of cell growth in both cell lines.
On the other hand, due to their ability to scavenge and reduce the production of free radicals, and because they act as transition metal chelators, flavonoids may exert a major chemo-preventive activity by protecting cells from various forms of oxidative stress and thus prevent cancer development. Naringenin possesses three hydroxyl groups in its aromatic rings which are responsible for its effective antioxidant activity. Some flavonoids such as naringenin were potent antimutagens. Thus, the antimutagenic effect of flavonoids may be the consequence of free radical scavenging and iron/copper chelation capacity. Prooxidative properties of flavonoids may also be involved in their ability to induce apoptosis through direct damage of DNA, RNA or protein in the cells. The prooxidant activity of flavonoids may be related to their ability to undergo autoxidation catalyzed by transition metals to produce superoxide anions (O2•).Polyphenols are considered to be complicated antioxidants which possess one, or numerous, benzene rings that bear one, or several, hydroxyl groups. Since polyphenols are redox-sensitive compounds and can also act as pro-oxidants, enhancing reactive oxygen species production, thus reducing cell growth. In order to estimate the efficacy of ellagic acid to induce cell death and apoptosis, we analyzed the genes related to apoptosis after 48 hours treatment of ellagic acid on HepG2 and MCF-7 in comparison to doxorubicin. The current work indicated that ellagic acid activates mitochondria-related apoptosis in MCF-7 cancerous cells and cell death was induced in HepG2 cell line. Anticancer agents, in particular phytochemicals help in up-regulation of pro-apoptotic genes and down-regulation of anti-apoptotic genes in cancer cells followed by induction of cell death and apoptosis.
In addition to caspase-dependent apoptosis, caspase-independent forms of cell death may also play a vital role in cancer treatment. Ellagic acid is a monomer that has been shown to act as potent antimutagenic agent against a variety of pro-mutagen through the interfere with the metabolic activity as blocking agents (Okmen and Turkcan, 2014). Amygdalin is a cyanogenic glycoside that possesses a low antioxidant activity. It has an anticancer activity through release of toxic cyanide that kill the cancer cells.