Enzymatic synthesis of DHA-lysophosphatidylcholine and evaluation of its effect on the MDA-MB-231 human breast cancer cell line
This work studies the synthesis of DHA-lysophosphatidylcholine (LPC-DHA) by solvent-free lipase-catalyzed esterification and the ability of LPC-DHA to reduce cell viability of the human cancer cell line MDA-MB-231. Optimization of esterification parameters between glycerophosphatidylcholine (GPC) an...
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2022
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Online Access: | https://theses.hal.science/tel-03934821 https://theses.hal.science/tel-03934821/document https://theses.hal.science/tel-03934821/file/2022LEMA1003.pdf |
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ftccsdartic:oai:HAL:tel-03934821v1 2024-02-11T09:55:42+01:00 Enzymatic synthesis of DHA-lysophosphatidylcholine and evaluation of its effect on the MDA-MB-231 human breast cancer cell line Synthèse enzymatique de la DHA-lysophosphatidylcholine et évaluation de son effet sur la lignée cellulaire de cancer du sein humain MDA-MB 231 Mohamad Ali, Dalal Biologie des Organismes, Stress, Santé, Environnement Le Mans Université (BiOSSE) Le Mans Université (UM) Le Mans Université Lionel Ulmann Gaëlle Pencreac'h Laurent Poisson 2022-02-22 https://theses.hal.science/tel-03934821 https://theses.hal.science/tel-03934821/document https://theses.hal.science/tel-03934821/file/2022LEMA1003.pdf en eng HAL CCSD NNT: 2022LEMA1003 tel-03934821 https://theses.hal.science/tel-03934821 https://theses.hal.science/tel-03934821/document https://theses.hal.science/tel-03934821/file/2022LEMA1003.pdf info:eu-repo/semantics/OpenAccess https://theses.hal.science/tel-03934821 Cellular Biology. Le Mans Université, 2022. English. ⟨NNT : 2022LEMA1003⟩ DHA-Lysophosphatidylcholine Solvent free esterification Immobilized lipase Design of experiments Response surface methodology MDA-MB-231 cell line Cell viability Cell death mechanisms Estérification sans solvant Lipase immobilisée Plan d'expériences Méthode de réponse de surface Lignée cellulaire MDA-MB-231 Viabilité cellulaire Mécanismes de mort cellulaire [SDV.BC]Life Sciences [q-bio]/Cellular Biology [CHIM.THER]Chemical Sciences/Medicinal Chemistry info:eu-repo/semantics/doctoralThesis Theses 2022 ftccsdartic 2024-01-14T00:02:41Z This work studies the synthesis of DHA-lysophosphatidylcholine (LPC-DHA) by solvent-free lipase-catalyzed esterification and the ability of LPC-DHA to reduce cell viability of the human cancer cell line MDA-MB-231. Optimization of esterification parameters between glycerophosphatidylcholine (GPC) and docosahexaenoic acid (DHA) was performed using response surface methodology (RSM). Two responses were measured: the conversion yield of GPC and the concentration of LPC-DHA in the medium. A GPC conversion yield of 67% is obtained under the following reaction conditions: a DHA/GPC molar ratio of 17, a reaction temperature of 36°C and a Novozym® 435 (immobilized lipase B from Candida antarctica) load of 15%. The maximum concentration of LPC-DHA obtained is 245 mM under the following conditions: a DHA/GPC molar ratio of 4, temperature of 36°C and a Novozym® 435 load of 15%. NMR characterization confirmed that the synthesized compound is pure and unoxidized sn-1 LPC-DHA In vitro study of the effect of different LPCs and different lipid vectors of DHA on MDA-MB-231 showed that LPC-DHA was the most effective in reducing cell viability, with IC50 for LPC-DHA, PC-DHA, MAG-DHA, and free DHA of 19 µM, 50 µM, 300 µM, and 347 µM, respectively. LPC-DHA and PC-DHA reduce cell viability primarily by inducing oxidative stress and plasma membrane damage. DHA and MAG-DHA also induced oxidative stress. In conclusion, this work led to the synthesis of LPC-DHA under favorable conditions and demonstrated the very interesting effect of LPC-DHA in reducing the viability of MDA-MB-231 breast cancer cells. Ce travail étudie la synthèse de DHA-lysophosphatidylcholine (LPC-DHA) par estérification enzymatique, catalysée par une lipase et sans solvant, ainsi que la capacité de la LPC-DHA à réduire la viabilité cellulaire de la lignée cancéreuse humaine MDA-MB-231. Une optimisation des paramètres de l’estérification entre la glycerophosphatidylcholine (GPC) et l’acide docosahexaénoïque (DHA, C22 :6 -3) a été réalisée selon la méthodologie des ... Doctoral or Postdoctoral Thesis Antarc* Antarctica Archive ouverte HAL (Hyper Article en Ligne, CCSD - Centre pour la Communication Scientifique Directe) |
institution |
Open Polar |
collection |
Archive ouverte HAL (Hyper Article en Ligne, CCSD - Centre pour la Communication Scientifique Directe) |
op_collection_id |
ftccsdartic |
language |
English |
topic |
DHA-Lysophosphatidylcholine Solvent free esterification Immobilized lipase Design of experiments Response surface methodology MDA-MB-231 cell line Cell viability Cell death mechanisms Estérification sans solvant Lipase immobilisée Plan d'expériences Méthode de réponse de surface Lignée cellulaire MDA-MB-231 Viabilité cellulaire Mécanismes de mort cellulaire [SDV.BC]Life Sciences [q-bio]/Cellular Biology [CHIM.THER]Chemical Sciences/Medicinal Chemistry |
spellingShingle |
DHA-Lysophosphatidylcholine Solvent free esterification Immobilized lipase Design of experiments Response surface methodology MDA-MB-231 cell line Cell viability Cell death mechanisms Estérification sans solvant Lipase immobilisée Plan d'expériences Méthode de réponse de surface Lignée cellulaire MDA-MB-231 Viabilité cellulaire Mécanismes de mort cellulaire [SDV.BC]Life Sciences [q-bio]/Cellular Biology [CHIM.THER]Chemical Sciences/Medicinal Chemistry Mohamad Ali, Dalal Enzymatic synthesis of DHA-lysophosphatidylcholine and evaluation of its effect on the MDA-MB-231 human breast cancer cell line |
topic_facet |
DHA-Lysophosphatidylcholine Solvent free esterification Immobilized lipase Design of experiments Response surface methodology MDA-MB-231 cell line Cell viability Cell death mechanisms Estérification sans solvant Lipase immobilisée Plan d'expériences Méthode de réponse de surface Lignée cellulaire MDA-MB-231 Viabilité cellulaire Mécanismes de mort cellulaire [SDV.BC]Life Sciences [q-bio]/Cellular Biology [CHIM.THER]Chemical Sciences/Medicinal Chemistry |
description |
This work studies the synthesis of DHA-lysophosphatidylcholine (LPC-DHA) by solvent-free lipase-catalyzed esterification and the ability of LPC-DHA to reduce cell viability of the human cancer cell line MDA-MB-231. Optimization of esterification parameters between glycerophosphatidylcholine (GPC) and docosahexaenoic acid (DHA) was performed using response surface methodology (RSM). Two responses were measured: the conversion yield of GPC and the concentration of LPC-DHA in the medium. A GPC conversion yield of 67% is obtained under the following reaction conditions: a DHA/GPC molar ratio of 17, a reaction temperature of 36°C and a Novozym® 435 (immobilized lipase B from Candida antarctica) load of 15%. The maximum concentration of LPC-DHA obtained is 245 mM under the following conditions: a DHA/GPC molar ratio of 4, temperature of 36°C and a Novozym® 435 load of 15%. NMR characterization confirmed that the synthesized compound is pure and unoxidized sn-1 LPC-DHA In vitro study of the effect of different LPCs and different lipid vectors of DHA on MDA-MB-231 showed that LPC-DHA was the most effective in reducing cell viability, with IC50 for LPC-DHA, PC-DHA, MAG-DHA, and free DHA of 19 µM, 50 µM, 300 µM, and 347 µM, respectively. LPC-DHA and PC-DHA reduce cell viability primarily by inducing oxidative stress and plasma membrane damage. DHA and MAG-DHA also induced oxidative stress. In conclusion, this work led to the synthesis of LPC-DHA under favorable conditions and demonstrated the very interesting effect of LPC-DHA in reducing the viability of MDA-MB-231 breast cancer cells. Ce travail étudie la synthèse de DHA-lysophosphatidylcholine (LPC-DHA) par estérification enzymatique, catalysée par une lipase et sans solvant, ainsi que la capacité de la LPC-DHA à réduire la viabilité cellulaire de la lignée cancéreuse humaine MDA-MB-231. Une optimisation des paramètres de l’estérification entre la glycerophosphatidylcholine (GPC) et l’acide docosahexaénoïque (DHA, C22 :6 -3) a été réalisée selon la méthodologie des ... |
author2 |
Biologie des Organismes, Stress, Santé, Environnement Le Mans Université (BiOSSE) Le Mans Université (UM) Le Mans Université Lionel Ulmann Gaëlle Pencreac'h Laurent Poisson |
format |
Doctoral or Postdoctoral Thesis |
author |
Mohamad Ali, Dalal |
author_facet |
Mohamad Ali, Dalal |
author_sort |
Mohamad Ali, Dalal |
title |
Enzymatic synthesis of DHA-lysophosphatidylcholine and evaluation of its effect on the MDA-MB-231 human breast cancer cell line |
title_short |
Enzymatic synthesis of DHA-lysophosphatidylcholine and evaluation of its effect on the MDA-MB-231 human breast cancer cell line |
title_full |
Enzymatic synthesis of DHA-lysophosphatidylcholine and evaluation of its effect on the MDA-MB-231 human breast cancer cell line |
title_fullStr |
Enzymatic synthesis of DHA-lysophosphatidylcholine and evaluation of its effect on the MDA-MB-231 human breast cancer cell line |
title_full_unstemmed |
Enzymatic synthesis of DHA-lysophosphatidylcholine and evaluation of its effect on the MDA-MB-231 human breast cancer cell line |
title_sort |
enzymatic synthesis of dha-lysophosphatidylcholine and evaluation of its effect on the mda-mb-231 human breast cancer cell line |
publisher |
HAL CCSD |
publishDate |
2022 |
url |
https://theses.hal.science/tel-03934821 https://theses.hal.science/tel-03934821/document https://theses.hal.science/tel-03934821/file/2022LEMA1003.pdf |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
https://theses.hal.science/tel-03934821 Cellular Biology. Le Mans Université, 2022. English. ⟨NNT : 2022LEMA1003⟩ |
op_relation |
NNT: 2022LEMA1003 tel-03934821 https://theses.hal.science/tel-03934821 https://theses.hal.science/tel-03934821/document https://theses.hal.science/tel-03934821/file/2022LEMA1003.pdf |
op_rights |
info:eu-repo/semantics/OpenAccess |
_version_ |
1790598333695262720 |