Biomimetic sulfated glycosaminoglycans maintain differentiation markers of breast epithelial cells and preferentially inhibit proliferation of cancer cells

Glycosaminoglycans (GAG) are key elements involved in various physiological and pathological processes including cancer. Several GAG-based drugs have been developed showing significant results and potential use as cancer therapeutics. We previously reported that alginate sulfate (AlgSulf), a GAG-mim...

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Bibliographic Details
Published in:Acta biomaterialia 2021-03, Vol.122, p.186-198
Main Authors: Habli, Zeina, Deen, Nataly Naser Al, Malaeb, Waddah, Mahfouz, Nadine, Mermerian, Angela, Talhouk, Rabih, Mhanna, Rami
Format: Article
Language:English
Subjects:
Adenocarcinoma
Alginates
Alginic acid
Anticancer properties
Antigens, Differentiation
Antineoplastic drugs
Antitumor agents
Assaying
Binding
Biomimetics
Breast
Breast cancer
Bromodeoxyuridine
Cancer
Cell differentiation
Cell Proliferation
Chemotherapy
Drug development
Enzyme-linked immunosorbent assay
Epidermal growth factor
Epithelial Cells
Epithelium
Glycosaminoglycans
Growth factors
Growth rate
Heparin
Humans
Immunofluorescence
Insulin
Lung Neoplasms
Mammary gland
Nodules
Polysaccharides
Quartz crystal microbalance
Saccharides
Substrates
Sulfated alginates
Sulfation
Therapeutics
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Summary:Glycosaminoglycans (GAG) are key elements involved in various physiological and pathological processes including cancer. Several GAG-based drugs have been developed showing significant results and potential use as cancer therapeutics. We previously reported that alginate sulfate (AlgSulf), a GAG-mimetic, reduces the proliferation of lung adenocarcinoma cells. In this study, we evaluated the preferential effect of AlgSulf on tumorigenic and nontumorigenic mammary epithelial cells in 2D, 3D, and coculture conditions. AlgSulf were synthesized with different degrees of sulfation (DSs) varying from 0 to 2.7 and used at 100 µg/mL on HMT-3522 S1 (S1) nontumorigenic mammary epithelial cells and their tumorigenic counterparts HMT-3522 T4–2 (T4–2) cells. The anti-tumor properties of AlgSulf were assessed using trypan blue and bromodeoxyuridine proliferation (BrdU) assays, immunofluorescence staining and transwell invasion assay.  Binding of insulin and epidermal growth factor (EGF) to sulfated substrates was measured using QCM-D and ELISA. In 2D, the cell growth rate of cells treated with AlgSulf was consistently lower compared to untreated controls (p
ISSN:1742-7061
1878-7568
DOI:10.1016/j.actbio.2020.12.049