Document Details
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Document Type |
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Thesis |
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Document Title |
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Studying the Chemosensitization Effect of Piceatannol with L- asparaginase Produced by Escherichia coli on some Immunological Characteristics of Acute Lymphoblastic Leukemia دراسة تأثير التحفيز الكيميائي لماده البكتانول مع الاسبراجينيز المنتج بواسطه بكتيريا ايشيريشيا كولاي على بعض الخصائص المناعية لخلايا اللوكيميا الليمفاويه من النوع الحاد |
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Subject |
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Faculty of Sciences |
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Document Language |
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Arabic |
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Abstract |
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L-Asparaginase enzyme isolated from Escherichia coli has been commonly used in the treatment of Acute Lymphoblastic Leukemia (ALL). However, hypersensitivity reactions and silent inactivation have been clinically reported due to the generation of antibodies against E. coli-L-asparaginase. Piceatannol (PIC) a natural analog of resveratrol (RES) is a phytochemical compound found in passion fruit seeds. Several studies have been revealed that PIC can potentially suppress some chronic inflammation. Aim: to investigate the synergetic effects of L-asparaginase enzyme generated from E. coli (Kidrolase, and Oncospare) combined with PIC on some immunological characteristic and antitumor capability on ALL cell-line (Jurkat cell). Methods: ALL cell-line was cultured in vitro and treated with therapeutic enzyme alone and in combination with Piceatannol. The cytotoxicity and cell viability were evaluated by the WST-8 assay. Phenotypic characteristics, several proteins expressions, apoptotic inductions, and DNA cell cycle were determined using flow cytometry. Sensitization with enzyme preparation was conducted in vivo using BALB/C mice, and ELISA techniques were used to determine MCPT-1, IgG, IgE, and IgM levels in mice plasma following injection protocol. Moreover, several signaling genes expressions were investigated using RT-PCR. Result: The present data demonstrated that L-asparaginase and Piceatannol have enhanced anti-proliferative effects on ALL cells as detected by the WST-8 assay. Cells treated with enzyme preparation were also exhibited significant decrease in CD34, and CD117 associated with significant increase in CD38 surface markers. Beside that Notch-1, Jagged-1, and CXCR-4 protein expressions were also significantly decreased. On the other hand, enzyme combination with PIC increased the apoptotic percentages of treated cells compared to cells treated with enzyme alone. Interestingly, in-vivo sensitization with enzyme preparation indicated that mice treated with the combination had less allergenic responses than bacterial enzyme alone. This was assessed by lower plasma concentrations of IgG, IgE, IgM and mMCP-1 in mice injected with enzyme preparation than other injected groups. Additionally, cells treated with L-asparaginase and Piceatannol showed molecular changes in several gene expressions. Furthermore, preliminary results of genetic expression were showed a significant decrease Nothch-1, Jagged-1, BCL-2,NFĸB, and CXCR-4 which can lead to induction of apoptosis and tumor suppression. Conclusion: our data revealed that combining therapeutic enzyme with Piceatannol might improve current ALL treatment, although additional studies are required to introduce this preparation as potential candidate for improving ALL therapy. |
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Supervisor |
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Dr. Alia M. Aldahlawi |
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Thesis Type |
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Master Thesis |
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Publishing Year |
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1440 AH
2019 AD |
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Added Date |
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Monday, January 21, 2019 |
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Researchers
| تسنيم علي باصبرين | Basbrain, Tasneem Ali | Researcher | Master | |
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