Production, Purification and Cytotoxic Activity of Astins: Potential Chemotherapeutic Agents Against Malignant Pleural Mesothelioma
Godon, Héléna
Promotor(s) : Willems, Luc ; Jacques, Philippe
Date of defense : 26-Aug-2019 • Permalink : http://hdl.handle.net/2268.2/7753
Details
Title : | Production, Purification and Cytotoxic Activity of Astins: Potential Chemotherapeutic Agents Against Malignant Pleural Mesothelioma |
Author : | Godon, Héléna |
Date of defense : | 26-Aug-2019 |
Advisor(s) : | Willems, Luc
Jacques, Philippe |
Committee's member(s) : | Fickers, Patrick
Joris, Bernard Purcaro, Giorgia Sindic, Marianne Kar, Tambi |
Language : | English |
Discipline(s) : | Life sciences > Biotechnology Human health sciences > Oncology Life sciences > Biochemistry, biophysics & molecular biology |
Institution(s) : | Université de Liège, Liège, Belgique |
Degree: | Master en bioingénieur : chimie et bioindustries, à finalité spécialisée |
Faculty: | Master thesis of the Gembloux Agro-Bio Tech (GxABT) |
Abstract
[en] Astins, a family of cyclopeptides, produced by the endophytic fungus Cyanodermella asteris are known to possess antineoplastic activities. Within this family, astin G, F, C and A can be differentiated by the chlorination degree (0, 1 or 2) of their proline residue and by the addition of a hydroxyl group. The objectives of this work are the optimization of astin G production, the purification of produced astins by a simple 3-step purification process and the comparison of the cytotoxic activity of astins against malignant pleural mesothelioma cells. To enhance astin G production, two growth media (MEAlow and MEA3m), two pH values (pH 6.1 and 3.5), as well as bromide feeding (0.5M NaBr) have been investigated. Follow-up of the C. asteris culture over 67 days reveals that highest astin amounts and production rates are obtained by setting the pH at 3.5 in MEA3m medium in presence of bromide. The purification process consists in a solid-phase-extraction followed by two rounds of semi-preparative RP-HPLC. Data show that astin C displays a cytotoxic activity against mesothelioma cells. Therefore, Astin C could improve current treatments against malignant pleural mesothelioma.
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