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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ftunimainelemans:oai:HAL:tel-04102506v1 2024-02-04T09:55:55+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) Collectivités Locales Mayennaises Le Mans Université Lionel Ulmann Gaëlle Pencreac'h Laurent Poisson 2022-02-02 https://hal.science/tel-04102506 https://hal.science/tel-04102506/document https://hal.science/tel-04102506/file/Dalal%20Mohamad%20Ali%20-%20manuscrit%20du%20th%C3%A9se%202022.pdf en eng HAL CCSD NNT: 2022LEMA1003 tel-04102506 https://hal.science/tel-04102506 https://hal.science/tel-04102506/document https://hal.science/tel-04102506/file/Dalal%20Mohamad%20Ali%20-%20manuscrit%20du%20th%C3%A9se%202022.pdf info:eu-repo/semantics/OpenAccess https://hal.science/tel-04102506 Biochemistry, Molecular Biology. Le Mans Université, 2022. English. ⟨NNT : 2022LEMA1003⟩ DHA-lysophosphatidylcholine Solvent free esterification Immobilized lipase Design of experiments (RSM) MDA-MB-231 cell line Breast cancer Cell death mechanisms Docosahexaenoic ω3 polyunsaturated fatty acid Responce surface methodology Estérification sans solvant Plan d’expérience (RSM) Lignée cellulaire MDA-MB-231 Cancer du sein Mort cellulaire Synthèse enzymatique Méthode de réponse de surface [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology [SDV.BC]Life Sciences [q-bio]/Cellular Biology [SDV.BIO]Life Sciences [q-bio]/Biotechnology info:eu-repo/semantics/doctoralThesis Theses 2022 ftunimainelemans 2024-01-10T17:37:12Z 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, 170 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 ω-3) a été réalisée selon la méthodologie des ... Doctoral or Postdoctoral Thesis Antarc* Antarctica Le Mans Université: Archives Ouvertes (HAL) |
institution |
Open Polar |
collection |
Le Mans Université: Archives Ouvertes (HAL) |
op_collection_id |
ftunimainelemans |
language |
English |
topic |
DHA-lysophosphatidylcholine Solvent free esterification Immobilized lipase Design of experiments (RSM) MDA-MB-231 cell line Breast cancer Cell death mechanisms Docosahexaenoic ω3 polyunsaturated fatty acid Responce surface methodology Estérification sans solvant Plan d’expérience (RSM) Lignée cellulaire MDA-MB-231 Cancer du sein Mort cellulaire Synthèse enzymatique Méthode de réponse de surface [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology [SDV.BC]Life Sciences [q-bio]/Cellular Biology [SDV.BIO]Life Sciences [q-bio]/Biotechnology |
spellingShingle |
DHA-lysophosphatidylcholine Solvent free esterification Immobilized lipase Design of experiments (RSM) MDA-MB-231 cell line Breast cancer Cell death mechanisms Docosahexaenoic ω3 polyunsaturated fatty acid Responce surface methodology Estérification sans solvant Plan d’expérience (RSM) Lignée cellulaire MDA-MB-231 Cancer du sein Mort cellulaire Synthèse enzymatique Méthode de réponse de surface [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology [SDV.BC]Life Sciences [q-bio]/Cellular Biology [SDV.BIO]Life Sciences [q-bio]/Biotechnology 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 (RSM) MDA-MB-231 cell line Breast cancer Cell death mechanisms Docosahexaenoic ω3 polyunsaturated fatty acid Responce surface methodology Estérification sans solvant Plan d’expérience (RSM) Lignée cellulaire MDA-MB-231 Cancer du sein Mort cellulaire Synthèse enzymatique Méthode de réponse de surface [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology [SDV.BC]Life Sciences [q-bio]/Cellular Biology [SDV.BIO]Life Sciences [q-bio]/Biotechnology |
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, 170 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 ω-3) a été réalisée selon la méthodologie des ... |
author2 |
Biologie des Organismes, Stress, Santé, Environnement Le Mans Université (BiOSSE) Le Mans Université (UM) Collectivités Locales Mayennaises 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://hal.science/tel-04102506 https://hal.science/tel-04102506/document https://hal.science/tel-04102506/file/Dalal%20Mohamad%20Ali%20-%20manuscrit%20du%20th%C3%A9se%202022.pdf |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
https://hal.science/tel-04102506 Biochemistry, Molecular Biology. Le Mans Université, 2022. English. ⟨NNT : 2022LEMA1003⟩ |
op_relation |
NNT: 2022LEMA1003 tel-04102506 https://hal.science/tel-04102506 https://hal.science/tel-04102506/document https://hal.science/tel-04102506/file/Dalal%20Mohamad%20Ali%20-%20manuscrit%20du%20th%C3%A9se%202022.pdf |
op_rights |
info:eu-repo/semantics/OpenAccess |
_version_ |
1789960146058739712 |