Ciampelli Cristina, Mangani Sylvia, Nieddu Gabriele, Formato Marilena, Ioannou Paraskevi, Kremmydas Spyros, Karamanos Nikos, Lepedda Antonio Junior
Department of Biomedical Sciences, University of Sassari, Viale San Pietro, 43b, 07100 Sassari, Italy.
Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26504 Patras, Greece.
Biology (Basel). 2025 Mar 25;14(4):334. doi: 10.3390/biology14040334.
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 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 -derived APs as promising antineoplastic agents, warranting further investigation into their mechanisms of action and structural characterization.
海洋无脊椎动物，尤其是海参，已成为具有潜在抗癌特性的生物活性化合物的宝贵来源。在本研究中，我们研究了来自海参物种的两种富含酸性多糖（APs）的组分（Ht1和Ht2）对高侵袭性细胞系MDA-MB-231的影响。进行了功能测定以评估细胞活力、迁移潜力、在I型胶原上的黏附以及细胞形态，并进行了基因表达分析。此外，还对它们对三维乳腺癌细胞衍生球体的影响进行了初步评估。两种AP组分均通过降低细胞活力发挥抗癌作用。Ht1对细胞迁移显示出显著的抑制作用，增加了在I型胶原上的黏附，并呈现出将间充质MDA-MB-231细胞转变为更上皮样表型的趋势。用AP组分处理调节了基因的表达，例如上皮标志物E-钙黏蛋白（对于Ht1），一种关键的细胞黏附分子，以及基质金属蛋白酶7和9（对于Ht2），参与细胞外基质重塑的酶，它们在癌症进展和转移中起关键作用。对球体未观察到显著影响，可能是由于APs的高电荷和亲水性，导致其难以渗透到球体内部层。尽管是初步的，但这些发现突出了源自海参的APs作为有前景的抗肿瘤剂的潜力，值得进一步研究其作用机制和结构特征。
