The anti-cancer properties of heparin and its derivatives: a review and prospect

Ma, Sainan; Mao, Zhixiang; Wu, Yang; Liang, Mingxing; Wang, Dandan; Chen, Xiu; Chang, Ping‐An; Zhang, Wei; Tang, Jinhai

doi:10.1080/19336918.2020.1767489

Cited by 71 publications

(60 citation statements)

References 78 publications

(95 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…GAGs have been demonstrated to modulate numerous biological processes, ranging from embryonic development, regulation of enzymatic activities, extracellular matrix assembly, and ligand binding to receptors to the regulation of cell signaling, through the regulation of distinct proteins, such as growth factors, chemokines, and adhesion molecules ( Vallet et al, 2021 ). These processes are particularly important when related to diseases, including cardiovascular disease ( Wight, 2018 ), cancer ( Ma et al, 2020 ), infectious diseases ( Kamhi et al, 2013 ), neurodegenerative diseases ( Huynh et al, 2019 ), inflammatory responses ( Morla, 2019 ), and wound healing ( Salbach et al, 2012 ). A schematic representation of the structure of GAGs and their interactions with proteins and functions relevant to specific diseases is shown in Figure 1 .…”

Section: Introductionmentioning

confidence: 99%

Glycosaminoglycan-Protein Interactions and Their Roles in Human Disease

Shi

Sheng

Chi

2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

Glycosaminoglycans (GAGs) are a family of linear and negatively charged polysaccharides that exist ubiquitously on the human cell surface as well as in the extracellular matrix. GAGs interact with a wide range of proteins, including proteases, growth factors, cytokines, chemokines and adhesion molecules, enabling them to mediate many physiological processes, such as protein function, cellular adhesion and signaling. GAG-protein interactions participate in and intervene in a variety of human diseases, including cardiovascular disease, infectious disease, neurodegenerative diseases and tumors. The breakthrough in analytical tools and approaches during the last two decades has facilitated a greater understanding of the importance of GAG-protein interactions and their roles in human diseases. This review focuses on aspects of the molecular basis and mechanisms of GAG-protein interactions involved in human disease. The most recent advances in analytical tools, especially mass spectrometry-based GAG sequencing and binding motif characterization methods, are introduced. An update of selected families of GAG binding proteins is presented. Perspectives on development of novel therapeutics targeting specific GAG-protein interactions are also covered in this review.

show abstract

Section: Introductionmentioning

confidence: 99%

Glycosaminoglycan-Protein Interactions and Their Roles in Human Disease

Shi

Sheng

Chi

2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“… 18 There are some pieces of evidence which suggest that heparin and heparinoids are involved in the suppression of cancer enhancement through serving the potent anti-cancer agent. 19 Heparin and these different types of GAGs are present in both extracellular and intracellular compartments of the cell. Heparin and associated different types of GAGs had been reported to accelerate the aggregation of various intracellularly existing peptide hormones.…”

Section: Introductionmentioning

confidence: 99%

Heparin Accelerates the Protein Aggregation via the Downhill Polymerization Mechanism: Multi-Spectroscopic Studies to Delineate the Implications on Proteinopathies

et al. 2021

View full text Add to dashboard Cite

Heparin is one of the members of the glycosaminoglycan (GAG) family, which has been associated with protein aggregation diseases including Alzheimer’s disease, Parkinson’s disease, and prion diseases. Here, we investigate heparin-induced aggregation of bovine serum albumin (BSA) using different spectroscopic techniques [absorption, 8-anilino-1-naphthalene sulfonic acid (ANS) and thioflavin T (ThT) fluorescence binding, and far- and near-UV circular dichroism]. Kinetic measurements revealed that heparin is involved in the significant enhancement of aggregation of BSA. The outcomes showed dearth of the lag phase and a considerable change in rate constant, which provides conclusive evidence, that is, heparin-induced BSA aggregation involves the pathway of the downhill polymerization mechanism. Heparin also causes enhancement of fluorescence intensity of BSA significantly. Moreover, heparin was observed to form amyloids and amorphous aggregates of BSA which were confirmed by ThT and ANS fluorescence, respectively. Circular dichroism measurements exhibit a considerable change in the secondary and tertiary structure of the protein due to heparin. In addition, binding studies of heparin with BSA to know the cause of aggregation, isothermal titration calorimetry measurements were exploited, from which heparin was observed to promote the aggregation of BSA by virtue of electrostatic interactions between positively charged amino acid residues of protein and negatively charged groups of GAG. The nature of binding of heparin with BSA is very much apparent with an appreciable heat of interaction and is largely exothermic in nature. Moreover, the Gibbs free energy change (ΔG) is negative, which indicates spontaneous nature of binding, and the enthalpy change (ΔH) and entropy change (ΔS) are also largely negative, which suggest that the interaction is driven by hydrogen bonding.

show abstract

“…In addition to APAP overdose and I/R injury, heparin/HS are also found to reduce inflammation by lowering pro-inflammatory cytokines and maintaining ECM in CCL4-induced liver fibrosis [ 67 ], doxorubicin-induced liver damage [ 68 ], and primary graft dysfunction in liver transplantation [ 69 ]. Moreover, heparin/HS also have additional therapeutic potential for its antitumor, antivirus, and anti-hepcidin effects; reviews on these topics can be found elsewhere [ 70 , 71 , 72 , 73 ]. Briefly, heparin prevents tumor metastasis possibly by reducing adhesion, proliferation, and migration of cancer cells by targeting adhesion molecules (P-selectin, VCAM-1) or chemokines (CXCL12) in preclinical studies [ 71 ].…”

Section: The Potentials For Hs-based Therapeuticsmentioning

confidence: 99%

“…Moreover, heparin/HS also have additional therapeutic potential for its antitumor, antivirus, and anti-hepcidin effects; reviews on these topics can be found elsewhere [ 70 , 71 , 72 , 73 ]. Briefly, heparin prevents tumor metastasis possibly by reducing adhesion, proliferation, and migration of cancer cells by targeting adhesion molecules (P-selectin, VCAM-1) or chemokines (CXCL12) in preclinical studies [ 71 ]. However, the existing data in clinical trials does not support the antimetastatic effect of heparin [ 74 ].…”

Section: The Potentials For Hs-based Therapeuticsmentioning

confidence: 99%

Potential Use of Anti-Inflammatory Synthetic Heparan Sulfate to Attenuate Liver Damage

Arnold

Liao

2020

Biomedicines

View full text Add to dashboard Cite

Heparan sulfate is a highly sulfated polysaccharide abundant on the surface of hepatocytes and surrounding extracellular matrix. Emerging evidence demonstrates that heparan sulfate plays an important role in neutralizing the activities of proinflammatory damage associate molecular patterns (DAMPs) that are released from hepatocytes under pathological conditions. Unlike proteins and nucleic acids, isolation of homogenous heparan sulfate polysaccharides from biological sources is not possible, adding difficulty to study the functional role of heparan sulfate. Recent advancement in the development of a chemoenzymatic approach allows production of a large number of structurally defined oligosaccharides. These oligosaccharides are used to probe the physiological functions of heparan sulfate in liver damage under different pathological conditions. The findings provide a potential new therapeutic agent to treat liver diseases that are associated with excessive inflammation.

show abstract

The anti-cancer properties of heparin and its derivatives: a review and prospect

Cited by 71 publications

References 78 publications

Glycosaminoglycan-Protein Interactions and Their Roles in Human Disease

Glycosaminoglycan-Protein Interactions and Their Roles in Human Disease

Heparin Accelerates the Protein Aggregation via the Downhill Polymerization Mechanism: Multi-Spectroscopic Studies to Delineate the Implications on Proteinopathies

Potential Use of Anti-Inflammatory Synthetic Heparan Sulfate to Attenuate Liver Damage

Contact Info

Product

Resources

About