Effects of Acidic Polysaccharide-Enriched Extracts from <i>Holothuria tubulosa</i> on Two- and Three-Dimensional Invasive Breast Cancer Cell Models

Marine invertebrates, particularly Holothurians, have emerged as valuable sources of bioactive compounds with potential anticancer properties. In this study, we investigated the effects of two acidic polysaccharide-enriched (APs) fractions (Ht1 and Ht2) from the sea cucumber species <i>Holothu...

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Main Authors: Cristina Ciampelli, Sylvia Mangani, Gabriele Nieddu, Marilena Formato, Paraskevi Ioannou, Spyros Kremmydas, Nikos Karamanos, Antonio Junior Lepedda
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/14/4/334
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author Cristina Ciampelli
Sylvia Mangani
Gabriele Nieddu
Marilena Formato
Paraskevi Ioannou
Spyros Kremmydas
Nikos Karamanos
Antonio Junior Lepedda
author_facet Cristina Ciampelli
Sylvia Mangani
Gabriele Nieddu
Marilena Formato
Paraskevi Ioannou
Spyros Kremmydas
Nikos Karamanos
Antonio Junior Lepedda
author_sort Cristina Ciampelli
collection DOAJ
description Marine invertebrates, particularly Holothurians, have emerged as valuable sources of bioactive compounds with potential anticancer properties. In this study, we investigated the effects of two acidic polysaccharide-enriched (APs) fractions (Ht1 and Ht2) from the sea cucumber species <i>Holothuria tubulosa</i> on the highly invasive cell line MDA-MB-231. Functional assays were performed to assess cell viability, migratory potential, adhesion on collagen I, and cell morphology, alongside gene expression analysis. Additionally, a preliminary evaluation of their effects on three-dimensional breast cancer cell-derived spheroids was conducted. Both AP fractions exerted anticancer effects by decreasing cell viability. Ht1 showed a significant inhibitory effect on cell migration, increased adhesion on collagen I, and exhibited a trend to transform the mesenchymal MDA-MB-231 cells to a more epithelial phenotype. Treatment with the AP fractions modulated the expression of genes, such as the epithelial marker E-cadherin (for the Ht1), a key cell adhesion molecule, and the matrix metalloproteinases 7 and 9 (for the Ht2), enzymes involved in extracellular matrix remodeling, which hold critical roles in cancer progression and metastasis. No significant effects were observed on spheroids, possibly due to the high charge and hydrophilicity of the APs, leading to poor penetration into the inner spheroid layers. Although preliminary, these findings highlight the potential of <i>H. tubulosa</i>-derived APs as promising antineoplastic agents, warranting further investigation into their mechanisms of action and structural characterization.
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spelling doaj-art-f98629571fe040e7b9cd6abd55e4100c2025-08-20T03:14:16ZengMDPI AGBiology2079-77372025-03-0114433410.3390/biology14040334Effects of Acidic Polysaccharide-Enriched Extracts from <i>Holothuria tubulosa</i> on Two- and Three-Dimensional Invasive Breast Cancer Cell ModelsCristina Ciampelli0Sylvia Mangani1Gabriele Nieddu2Marilena Formato3Paraskevi Ioannou4Spyros Kremmydas5Nikos Karamanos6Antonio Junior Lepedda7Department of Biomedical Sciences, University of Sassari, Viale San Pietro, 43b, 07100 Sassari, ItalyBiochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26504 Patras, GreeceDepartment of Biomedical Sciences, University of Sassari, Viale San Pietro, 43b, 07100 Sassari, ItalyDepartment of Biomedical Sciences, University of Sassari, Viale San Pietro, 43b, 07100 Sassari, ItalyBiochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26504 Patras, GreeceBiochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26504 Patras, GreeceBiochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26504 Patras, GreeceDepartment of Biomedical Sciences, University of Sassari, Viale San Pietro, 43b, 07100 Sassari, ItalyMarine invertebrates, particularly Holothurians, have emerged as valuable sources of bioactive compounds with potential anticancer properties. In this study, we investigated the effects of two acidic polysaccharide-enriched (APs) fractions (Ht1 and Ht2) from the sea cucumber species <i>Holothuria tubulosa</i> on the highly invasive cell line MDA-MB-231. Functional assays were performed to assess cell viability, migratory potential, adhesion on collagen I, and cell morphology, alongside gene expression analysis. Additionally, a preliminary evaluation of their effects on three-dimensional breast cancer cell-derived spheroids was conducted. Both AP fractions exerted anticancer effects by decreasing cell viability. Ht1 showed a significant inhibitory effect on cell migration, increased adhesion on collagen I, and exhibited a trend to transform the mesenchymal MDA-MB-231 cells to a more epithelial phenotype. Treatment with the AP fractions modulated the expression of genes, such as the epithelial marker E-cadherin (for the Ht1), a key cell adhesion molecule, and the matrix metalloproteinases 7 and 9 (for the Ht2), enzymes involved in extracellular matrix remodeling, which hold critical roles in cancer progression and metastasis. No significant effects were observed on spheroids, possibly due to the high charge and hydrophilicity of the APs, leading to poor penetration into the inner spheroid layers. Although preliminary, these findings highlight the potential of <i>H. tubulosa</i>-derived APs as promising antineoplastic agents, warranting further investigation into their mechanisms of action and structural characterization.https://www.mdpi.com/2079-7737/14/4/334marine invertebratesacidic polysaccharides (APs)anticancer propertiesbreast cancerepithelial–mesenchymal transition (EMT)
spellingShingle Cristina Ciampelli
Sylvia Mangani
Gabriele Nieddu
Marilena Formato
Paraskevi Ioannou
Spyros Kremmydas
Nikos Karamanos
Antonio Junior Lepedda
Effects of Acidic Polysaccharide-Enriched Extracts from <i>Holothuria tubulosa</i> on Two- and Three-Dimensional Invasive Breast Cancer Cell Models
Biology
marine invertebrates
acidic polysaccharides (APs)
anticancer properties
breast cancer
epithelial–mesenchymal transition (EMT)
title Effects of Acidic Polysaccharide-Enriched Extracts from <i>Holothuria tubulosa</i> on Two- and Three-Dimensional Invasive Breast Cancer Cell Models
title_full Effects of Acidic Polysaccharide-Enriched Extracts from <i>Holothuria tubulosa</i> on Two- and Three-Dimensional Invasive Breast Cancer Cell Models
title_fullStr Effects of Acidic Polysaccharide-Enriched Extracts from <i>Holothuria tubulosa</i> on Two- and Three-Dimensional Invasive Breast Cancer Cell Models
title_full_unstemmed Effects of Acidic Polysaccharide-Enriched Extracts from <i>Holothuria tubulosa</i> on Two- and Three-Dimensional Invasive Breast Cancer Cell Models
title_short Effects of Acidic Polysaccharide-Enriched Extracts from <i>Holothuria tubulosa</i> on Two- and Three-Dimensional Invasive Breast Cancer Cell Models
title_sort effects of acidic polysaccharide enriched extracts from i holothuria tubulosa i on two and three dimensional invasive breast cancer cell models
topic marine invertebrates
acidic polysaccharides (APs)
anticancer properties
breast cancer
epithelial–mesenchymal transition (EMT)
url https://www.mdpi.com/2079-7737/14/4/334
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