الفهرس 
Introduction & Aims of the StudyOnly 14 pages are availabe for public view
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Abstract
A better understanding of cancer biological processes such as growth, migration and metastasis has undergone evolutionary changes in cancer treatment protocols. Complete removal of cancer without inducing damage to the rest of the body, when it is applicable, is the ideal goal of treatment. Meanwhile, the ability of radiotherapy to induce cell death by generating cellular sudden oxidative stress resulting in DNA double strand breakage and cell apoptosis suggest its use as neo adjuvant therapy or complementary to surgical interference. However, a tumor response to radiation varies with cell repair capacity, oxygenation, and other factors. The severe side effects accompanied by Chemo and/or radio therapy direct the cancer biologist’s attention for the need of other alternatives such as naturally extracted phytochemical and immunotherapy for selective targeting therapy of cancer cells specifically in case of chemo or radio-resistant tumors. one of this phytochemicals is Artemisia Judaica (Shih Balady, family Asteraceae) is one of the common species of the genus Artemisia that grows in Sinai, Egypt. It is widely used in traditional medicine by Bedouins. In recent years, a lot of research has been done on this plant extract after it has proven effective as an antimicrobial, anticancer, and antioxidant. This study aimed to determine the anticancer characteristic of Artemisia extract (ART) on hepatic-cellular carcinoma cell line HepG2, and its potential role in sensitizing HepG2 cell line for radiotherapy. The work of the tests was divided into two periods, the first was after 24 hours of irradiation, while the second period was after 48 hours, when treatment was added for a period of 24 hours, and then left in the incubator for 24 hours before laboratory tests were conducted. molecular studies of the effects of ART and/or x-rays on HepG2 cells were conducted by sub-culturing the cells into eight groups for each group of treatment, whether it is 24 or 48 hours as follows: 1.Control group: HepG2 without treatment. 2.ART group: HepG2 treated with 69.25 µg/ml. 3.ART group: HepG2 treated with 34.625 µg/ml. 4.ART group: HepG2 treated with 17.3125 µg/ml. 5.IR control group: HepG2 irradiated with single dose of IR (2.5Gy). 6.ART + Rad (combined therapy) group: HepG2 treated with 69.25 µg/ml. 7.ART + Rad (combined therapy) group: HepG2 treated with 34.625 µg/ml. 8.ART +Rad (combined therapy) group: HepG2 treated with 17.3125 µg/ml. The following are the key finding from this study’s developed data: The first objective of the present work is to characterize the volatile components by GC/MS analysis, phytochemical components, and antioxidant activity of the ethanol extract of the leaves and stem issues of Artemisia Judaica. The ART also verified good contents of phenolic, and flavonoids in the phytochemical analysis. The plant extract in addition revealed good antioxidant activity (IC50 = 125.1±6.7 μM). Estimation of the cytotoxic effect of ART on HepG2 cells. The data showed a significant dose dependent cytotoxic effect of ART on HepG2 cells with IC50 calculated to be 138.5 µg/ml. In order to study the sensitizing effect of ART, HepG2 cells were subjected to (2.5 Gy) IR with/without pre-sensitization with ART The data revealed a significant effect in inhibiting cell growth indicated by the decrease at the developed colonies numbers and size after 24 and 48 hr of treatment. Meanwhile, these data were further confirmed by cell cycle analyses assay which recorded a cell cycle arrest at G1 phase in all combined therapy group compared to ART and control groups. molecular validation of the ART and/or IR dependent induction of HepG2 cell apoptosis was illustrated via upregulation at the expression of pro apoptotic Bax and downregulation of Bcl2 proteins in treated cells compared to control group. The analyses of Bax/Bcl2 transcripts ratio indicated a significant induction of cell apoptosis in many groups of treatment compared to control. The effect of ART, IR, and ART plus IR on the ability of HepG2 to migrate into distant organs, was assessed using a wound healing assay. The combined therapy showed a profound effect in inhibiting the ability of HepG2 cells to migrate into the induced wound. The anti-metastatic ability of Art and/or IR was molecularly validated by the significant effect of ART, IR and combined groups, except for 34.625+IR group, to diminish CD44 expression after treatment for 24 hrs. Interestingly, after treatment for 48 hrs. CD44 expression was significantly downregulated only in IR and 17.3 +IR groups compared to control group. Which can be explain by the entrance of the cells in apoptotic pathway. These data were confirmed by the downregulation of MMP9 compared to control group after treatment for 24 hrs. indicating the role of ART in sensitizing HepG2 cells to IR. Meanwhile, the expression of TNFα as an upstream regulatory of CD44 expression was significantly downregulated in all groups compared to control group after treatment for 24 hrs. The ability of cancer to upregulated the antioxidant enzymes expression is one of the main mechanism that use to resist the upraising of free radicals which are the main effect of ionizing radiation therapy. finally, the mechanism of ART in sensitizing HPG2 cells to x-rays was tested by elucidating its role in downregulating NRF2 gene expression. After 48 hr. and unlike to 24 hr period of treatment, the expression of NRF2 transcripts was significantly downregulated in all groups except for 34.625 group compared to control. NRF2 help in regulating the work of antioxidant enzymes that can help at the protection against oxidative damage. This oxidative damage can be triggered by injury and inflammation and involves in the production of free radicals. The reduction at NRF2 levels led to a decrease at the cells’ ability for migration and metastasis. The wide majority of tests showed that there was an effect of the radiation-exposed groups compared with the radiation control group, and this enhances the ability of the combined treatment to increase the sensitivity of liver cancer cells to ionizing radiation.