Antiproliferative Properties of Scandium Exopolysaccharide Complexes on Several Cancer Cell Lines

Antimetastatic properties on both murine and human osteosarcoma cell lines (POS-1 and KHOS) have been evidenced using exopolysaccharide (EPS) derivatives, produced by <i>Alteromonas infernus</i> bacterium. These derivatives had no significant effect on the cell cycle neither a pro-apopto...

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Main Authors: Javier Muñoz-Garcia, Mattia Mazza, Cyrille Alliot, Corinne Sinquin, Sylvia Colliec-Jouault, Dominique Heymann, Sandrine Huclier-Markai
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Marine Drugs
Subjects:
Online Access:https://www.mdpi.com/1660-3397/19/3/174
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author Javier Muñoz-Garcia
Mattia Mazza
Cyrille Alliot
Corinne Sinquin
Sylvia Colliec-Jouault
Dominique Heymann
Sandrine Huclier-Markai
author_facet Javier Muñoz-Garcia
Mattia Mazza
Cyrille Alliot
Corinne Sinquin
Sylvia Colliec-Jouault
Dominique Heymann
Sandrine Huclier-Markai
author_sort Javier Muñoz-Garcia
collection DOAJ
description Antimetastatic properties on both murine and human osteosarcoma cell lines (POS-1 and KHOS) have been evidenced using exopolysaccharide (EPS) derivatives, produced by <i>Alteromonas infernus</i> bacterium. These derivatives had no significant effect on the cell cycle neither a pro-apoptotic effect on osteosarcoma cells. Based on this observation, these EPSs could be employed as new drug delivery systems for therapeutic uses. A theranostic approach, i.e., combination of a predictive biomarker with a therapeutic agent, has been developed notably by combining with true pair of theranostic radionuclides, such as scandium <sup>47</sup>Sc/<sup>44</sup>Sc. However, it is crucial to ensure that, once complexation is done, the biological properties of the vector remain intact, allowing the molecular tropism of the ligand to recognize its molecular target. It is important to assess if the biological properties of EPS evidenced on osteosarcoma cell lines remain when scandium is complexed to the polymers and can be extended to other cancer cell types. Scandium-EPS complexes were thus tested in vitro on human cell lines: MNNG/HOS osteosarcoma, A375 melanoma, A549 lung adenocarcinoma, U251 glioma, MDA231 breast cancer, and Caco2 colon cancer cells. An xCELLigence Real Cell Time Analysis (RTCA) technology assay was used to monitor for 160 h, the proliferation kinetics of the different cell lines. The tested complexes exhibited an anti-proliferative effect, this effect was more effective compared to EPS alone. This increase of the antiproliferative properties was explained by a change in conformation of EPS complexes due to their polyelectrolyte nature that was induced by complexation. Alterations of both growth factor-receptor signaling, and transmembrane protein interactions could be the principal cause of the antiproliferative effect. These results are very promising and reveal that EPS can be coupled to scandium for improving its biological effects and also suggesting that no major structural modification occurs on the ligand.
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spelling doaj.art-b6a29497cee2436799cb219529f3a4202023-11-21T11:38:05ZengMDPI AGMarine Drugs1660-33972021-03-0119317410.3390/md19030174Antiproliferative Properties of Scandium Exopolysaccharide Complexes on Several Cancer Cell LinesJavier Muñoz-Garcia0Mattia Mazza1Cyrille Alliot2Corinne Sinquin3Sylvia Colliec-Jouault4Dominique Heymann5Sandrine Huclier-Markai6Institut de Cancérologie de l’Ouest, Université de Nantes, Blvd Jacques Monod, F-44805 Saint-Herblain, FranceGIP ARRONAX, 1 rue Aronnax, CEDEX 3, F-44817 Nantes, FranceGIP ARRONAX, 1 rue Aronnax, CEDEX 3, F-44817 Nantes, FranceIFREMER, Institut Français de Recherche pour L’exploitation de la mer, rue de l’Ile d’Yeu, BP21105, CEDEX 3, F-44311 Nantes, FranceIFREMER, Institut Français de Recherche pour L’exploitation de la mer, rue de l’Ile d’Yeu, BP21105, CEDEX 3, F-44311 Nantes, FranceInstitut de Cancérologie de l’Ouest, Université de Nantes, Blvd Jacques Monod, F-44805 Saint-Herblain, FranceGIP ARRONAX, 1 rue Aronnax, CEDEX 3, F-44817 Nantes, FranceAntimetastatic properties on both murine and human osteosarcoma cell lines (POS-1 and KHOS) have been evidenced using exopolysaccharide (EPS) derivatives, produced by <i>Alteromonas infernus</i> bacterium. These derivatives had no significant effect on the cell cycle neither a pro-apoptotic effect on osteosarcoma cells. Based on this observation, these EPSs could be employed as new drug delivery systems for therapeutic uses. A theranostic approach, i.e., combination of a predictive biomarker with a therapeutic agent, has been developed notably by combining with true pair of theranostic radionuclides, such as scandium <sup>47</sup>Sc/<sup>44</sup>Sc. However, it is crucial to ensure that, once complexation is done, the biological properties of the vector remain intact, allowing the molecular tropism of the ligand to recognize its molecular target. It is important to assess if the biological properties of EPS evidenced on osteosarcoma cell lines remain when scandium is complexed to the polymers and can be extended to other cancer cell types. Scandium-EPS complexes were thus tested in vitro on human cell lines: MNNG/HOS osteosarcoma, A375 melanoma, A549 lung adenocarcinoma, U251 glioma, MDA231 breast cancer, and Caco2 colon cancer cells. An xCELLigence Real Cell Time Analysis (RTCA) technology assay was used to monitor for 160 h, the proliferation kinetics of the different cell lines. The tested complexes exhibited an anti-proliferative effect, this effect was more effective compared to EPS alone. This increase of the antiproliferative properties was explained by a change in conformation of EPS complexes due to their polyelectrolyte nature that was induced by complexation. Alterations of both growth factor-receptor signaling, and transmembrane protein interactions could be the principal cause of the antiproliferative effect. These results are very promising and reveal that EPS can be coupled to scandium for improving its biological effects and also suggesting that no major structural modification occurs on the ligand.https://www.mdpi.com/1660-3397/19/3/174exopolysaccharidesscandiumtheranosticcancer cell linesproliferation
spellingShingle Javier Muñoz-Garcia
Mattia Mazza
Cyrille Alliot
Corinne Sinquin
Sylvia Colliec-Jouault
Dominique Heymann
Sandrine Huclier-Markai
Antiproliferative Properties of Scandium Exopolysaccharide Complexes on Several Cancer Cell Lines
Marine Drugs
exopolysaccharides
scandium
theranostic
cancer cell lines
proliferation
title Antiproliferative Properties of Scandium Exopolysaccharide Complexes on Several Cancer Cell Lines
title_full Antiproliferative Properties of Scandium Exopolysaccharide Complexes on Several Cancer Cell Lines
title_fullStr Antiproliferative Properties of Scandium Exopolysaccharide Complexes on Several Cancer Cell Lines
title_full_unstemmed Antiproliferative Properties of Scandium Exopolysaccharide Complexes on Several Cancer Cell Lines
title_short Antiproliferative Properties of Scandium Exopolysaccharide Complexes on Several Cancer Cell Lines
title_sort antiproliferative properties of scandium exopolysaccharide complexes on several cancer cell lines
topic exopolysaccharides
scandium
theranostic
cancer cell lines
proliferation
url https://www.mdpi.com/1660-3397/19/3/174
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