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

Habli, Zeina; Deen, Nataly Naser Al; Malaeb, Waddah; Mahfouz, Nadine; Mermerian, Angela; Talhouk, Rabih; Mhanna, Rami

doi:10.1016/j.actbio.2020.12.049

Cited by 8 publications

(2 citation statements)

References 64 publications

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“…Proteoglycans (PGs), key components of the extracellular matrix, consist of one or more glycosaminoglycans (GAGs) covalently attached to a core protein. − GAGs are known to directly influence the cell cycle and contribute to neovascularization and the proliferation of malignant cells in tumors. − Capable of interacting with over 500 proteins, GAGs undergo substantial alterations in their molecular weight, distribution, composition, and modifications, such as sulfation, during cancer progression. − For instance, upregulation of chondroitin sulfate (CS) proteoglycan 4 expression has been reported in various cancers, including stage G2 and G3 of type I endometrial cancer, melanoma, soft-tissue sarcoma, and triple-negative breast cancer. − The involvement of PGs and GAGs in tumor development processes makes them promising targets for antitumor therapies. − …”

Section: Introductionmentioning

confidence: 99%

Discovery of Novel 2-Oxoacetamide Derivatives as B3GAT3 Inhibitors for the Treatment of Hepatocellular Carcinoma

Yin,

Zhang,

et al. 2024

J. Med. Chem.

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, overexpressed in hepatocellular carcinoma (HCC) and negatively correlated to prognosis, is a promising target for cancer therapy. Currently, no studies have reported small molecule inhibitors of B3GAT3. In this study, we designed and synthesized a series of small-molecule inhibitors of B3GAT3 through virtual screening and structure optimization. The lead compound TMLB-C16 exhibited potent B3GAT3 inhibitory activity (KD = 3.962 μM) by effectively suppressing proliferation and migration, and inducing cell cycle arrest and apoptosis in MHCC-97H (IC 50 = 6.53 ± 0.18 μM) and HCCLM3 (IC 50 = 6.22 ± 0.23 μM) cells. Furthermore, compound TMLB-C16 demonstrated favorable pharmacokinetic properties with a relatively high bioavailability of 68.37%. It significantly inhibited tumor growth in both MHCC-97H and HCCLM3 xenograft tumor models without causing obvious toxicity. These results indicate that compound TMLB-C16 is an effective small molecule inhibitor of B3GAT3, providing a basis for the future development of B3GAT3-targeted drugs.

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Section: Introductionmentioning

confidence: 99%

Discovery of Novel 2-Oxoacetamide Derivatives as B3GAT3 Inhibitors for the Treatment of Hepatocellular Carcinoma

Yin,

Zhang,

et al. 2024

J. Med. Chem.

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“…Immunofluorescent staining17 Frozen mouse heart sections, H9C2 cell line or PNRCs were fixed with 4% paraformaldehyde (PFA), permeabilized with 0.5% Triton X-100 in PBS, and blocked with 5% bovine serum album (BSA) before incubation with rabbit anti-p-NFκB(1:200 dilution, Affinity Biosciences, OH), rabbit anti-actin (1:200 dilution, Abcam, Inc., Cambridge, MA), rabbit anti-cTNT (1:400 dilution, Abcam, Inc., Cambridge, MA), rabbit anti-TNF-α (1:200 dilution, Abcam, Inc., Cambridge, MA), rabbit anti-IL-1β (1:200 dilution, Abcam, Inc., Cambridge, MA), rabbit anti-Bax (1:200 dilution, CST, Danvers, MA), rabbit anti-Bcl2 (1:200 dilution, CST, Danvers, MA), or rabbit anti-Caspase3 (1:200 dilution, Proteintech, Rosemont, IL). After incubated with Goat Antibody to Rabbit IgG -H&L (Alexa Fluor ® 594) (1:400 dilution, Abcam, Inc., Cambridge, MA) and Goat Antibody to Mouse IgG-H&L (Alexa Fluor ® 488) (1:400 dilution, Abcam, Inc., Cambridge, MA).…”

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confidence: 99%

Amelioratory effect of neoandrographolide on myocardial ischemic‐reperfusion injury by its anti‐inflammatory and anti‐apoptotic activities

Liu

Zhang

et al. 2021

Environmental Toxicology

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In the present study, we aimed to evaluate the cardioprotective effect of neoandrographolide (Neo) on myocardial ischemia/reperfusion injury (I/R) models and explore its possible mechanism. We randomly and equally divided male mice into sham-operation, I/R, and I/R + Neo groups. H9C2 cell line and primary neonatal rat cardiomyocytes were induced into the simulated I/R's status and used to further validate the Neo's role in vitro. Heart systolic function, indexes of myocardial injury (IMI), infarct size, pathological change, cell apoptosis, inflammatory cytokines, and indexes related to apoptotic and NF-κB signaling pathways were analyzed in vivo or in vitro after the Neo treatment. Compared to the I/R group, Neo significantly suppressed IMI, infarct size, inflammatory cell infiltration, cell apoptosis, inflammatory cytokines, bax, cleaved caspase-3, P-IKBa, and P-NF-κB protein expressions, and the translocation of NF-kB subunit p65 from the cytoplasm to the nucleus in vivo or in vitro. Still, ejected fraction, fractional shortening, and the bcl-2 protein expression were notably increased after the Neo treatment. Neo could be developed into a new drug for treating myocardial I/R by inhibiting myocardial inflammation and apoptosis, which was closely related to suppressing the activation of bax/bcl-2 and NF-κB signaling pathways.

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Sulfated Alginate for Biomedical Applications

Mutch,

Yang,

Ferro

et al. 2024

Macromolecular Bioscience

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Alginate (Alg) polymers have received much attention due to the mild conditions required for gel formation and their good bio‐acceptability. However, due to limited interactions with cells, many drugs, and biomolecules, chemically modified alginates are of great interest. Sulfated alginate (S–Alg) is a promising heparin‐mimetic that continues to be investigated both as a drug molecule and as a component of biomaterials. Herein, the S–Alg literature of the past five years (2017–2023) is reviewed. Several methods used to synthesize S–Alg are described, with a focus on new advances in characterization and stereoselectivity. Material fabrication is another focus and spans bulk materials, particles, scaffolds, coatings, and part of multicomponent biomaterials. The new application of S–Alg as an antitumor agent is highlighted together with studies evaluating safety and biodistribution. The high binding affinity of S–Alg for various drugs and heparin‐binding proteins is exploited extensively in biomaterial design to tune the encapsulation and release of these agents and this aspect is covered in detail. Recommondations include publishing key material properties to allow reproducibility, careful selection of appropriate sulfation strategies, the use of cross–linking strategies other than ionic cross–linking for material fabrication, and more detailed toxicity and biodistribution studies to inform future work.

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

Cited by 8 publications

References 64 publications

Discovery of Novel 2-Oxoacetamide Derivatives as B3GAT3 Inhibitors for the Treatment of Hepatocellular Carcinoma

Discovery of Novel 2-Oxoacetamide Derivatives as B3GAT3 Inhibitors for the Treatment of Hepatocellular Carcinoma

Amelioratory effect of neoandrographolide on myocardial ischemic‐reperfusion injury by its anti‐inflammatory and anti‐apoptotic activities

Sulfated Alginate for Biomedical Applications

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