Molecular Mechanisms Underlying the Anti-Breast Cancer Stem Cell Activity of <i>Pterocladia capillacea</i> and <i>Corallina officinalis</i> Polysaccharides

Author(s):

Hebatallah G. Hafez, Rafat M. Mohareb, Sohair M. Salem, Azza A. Matloub, Emad F. Eskander and Hanaa H. Ahmed*   Pages 1213 - 1225 ( 13 )

Abstract:

Objective: This study aimed to appraise the activity of <i>Pterocladia capillacea</i> and <i>Corallina officinalis</i> polysaccharides against Breast Cancer Stem Cells (BCSCs). <i>P. capillacea</i> and <i>C. officinalis</i> polysaccharides were characterized to be sulfated polysaccharide-protein complexes. <P> Methods: Cytotoxicity of the polysaccharides against MDA-MB-231 and MCF-7 cell lines along with their impact on CD44+/CD24− and aldehyde dehydrogenase 1(ALDH1) positive BCSC population were determined. Their effect on gene expression of CSC markers, Wnt/β-catenin and Notch signaling pathways was evaluated. <P> Results: <i>P. capillacea</i> and <i>C. officinalis</i> polysaccharides inhibited the growth of breast cancer cells and reduced BCSC subpopulation. <i>P. capillacea</i> polysaccharides significantly down-regulated OCT4, SOX2, ALDH1A3 and vimentin in MDA-MB-231 as well as in MCF-7 cells except for vimentin that was up-regulated in MCF-7 cells. <i>C. officinalis</i> polysaccharides exhibited similar effects except for OCT4 that was up-regulated in MDA-MB-231 cells. Significant suppression of Cyclin D1 gene expression was noted in MDA-MB-231 and MCF-7 cells treated with <i>P. capillacea</i> or <i>C. officinalis</i> polysaccharides. β-catenin and c-Myc genes were significantly down-regulated in MDA-MB-231 cells treated with C. officinalis and <i>P. capillacea</i> polysaccharides, respectively, while being up-regulated in MCF-7 cells treated with either of them. Additionally, <i>P. capillacea</i> and <i>C. officinalis</i> polysaccharides significantly down-regulated Hes1 gene in MCF-7 cells despite increasing Notch1 gene expression level. However, significant down-regulation of Notch1 gene was observed in MDA-MB-231 cells treated with </i>P. capillacea</i> polysaccharides. <P> Conclusion: Collectively, this study provides evidence for the effectiveness of <i>P. capillacea</i> and <i>C. officinalis</i> polysaccharides in targeting BCSCs through interfering with substantial signaling pathways contributing to their functionality.

Keywords:

<i>Pterocladia capillacea, Corallina officinalis</i>, polysaccharides, breast cancer stem cells, molecular signaling pathways, aldehyde dehydrogenase.

Affiliation:

Hormones Department, Medical Research Division, National Research Centre, Dokki, Giza, Chemistry Department, Faculty of Science, Cairo University, Cairo, Molecular Genetics and Enzymology Department, National Research Centre, Dokki, Giza, Department of Pharmacognosy, Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Giza, Hormones Department, Medical Research Division, National Research Centre, Dokki, Giza, Hormones Department, Medical Research Division, National Research Centre, Dokki, Giza

Graphical Abstract:

Read Full-Text article