Modified citrus pectin stops progression of liver fibrosis by inhibiting galectin-3 and inducing apoptosis of stellate cells

Abu-Elsaad, Nashwa; Elkashef, Wagdi

doi:10.1139/cjpp-2015-0284

Cited by 53 publications

(37 citation statements)

References 31 publications

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“…Anti-galectin mAbs and Gal-3 recombinant were also effective in vitro studies with diverse cell lines [240-242]. Other galectin inhibition methods that showed some success including inhibition of biosynthesis of tumor-associated antigens [243], use of modified citrus pectin (MCP) [244], small carbohydrate-based inhibitors, such as ß-galactosides [245], and multivalent and allosteric inhibitors, among others [232]. …”

Section: Discussionmentioning

confidence: 99%

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Silva-filho¹,

Sena²,

Lima

et al. 2017

Cell Physiol Biochem

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Post-translational and co-translational enzymatic addition of glycans (glycosylation) to proteins, lipids, and other carbohydrates, is a powerful regulator of the molecular machinery involved in cell cycle, adhesion, invasion, and signal transduction, and is usually seen in both in vivo and in vitro cancer models. Glycosyltransferases can alter the glycosylation pattern of normal cells, subsequently leading to the establishment and progression of several diseases, including cancer. Furthermore, a growing amount of research has shown that different oxygen tensions, mainly hypoxia, leads to a markedly altered glycosylation, resulting in altered glycan-receptor interactions. Alteration of intracellular glucose metabolism, from aerobic cellular respiration to anaerobic glycolysis, inhibition of integrin 3α1β translocation to the plasma membrane, decreased 1,2-fucosylation of cell-surface glycans, and galectin overexpression are some consequences of the hypoxic tumor microenvironment. Additionally, increased expression of gangliosides carrying N-glycolyl sialic acid can also be significantly affected by hypoxia. For all these reasons, it is possible to realize that hypoxia strongly alters glycobiologic events within tumors, leading to changes in their behavior. This review aims to analyze the complexity and importance of glycoconjugates and their molecular interaction network in the hypoxic context of many solid tumors.

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Section: Discussionmentioning

confidence: 99%

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Silva-filho¹,

Sena²,

Lima

et al. 2017

Cell Physiol Biochem

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“…Recently, another MCP compound, named PectaSol-C, was introduced and commercialized by EcoNugenics (Santa Rosa, CA, USA). It was demonstrated to be able to reduce Gal-3 serum levels in vivo in both mice [ 394 ] and humans [ 395 ].…”

Section: Tmentioning

confidence: 99%

Galectin-3: One Molecule for an Alphabet of Diseases, from A to Z

Sciacchitano

Lavra

Morgante

et al. 2018

IJMS

285

240

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Galectin-3 (Gal-3) regulates basic cellular functions such as cell–cell and cell–matrix interactions, growth, proliferation, differentiation, and inflammation. It is not surprising, therefore, that this protein is involved in the pathogenesis of many relevant human diseases, including cancer, fibrosis, chronic inflammation and scarring affecting many different tissues. The papers published in the literature have progressively increased in number during the last decades, testifying the great interest given to this protein by numerous researchers involved in many different clinical contexts. Considering the crucial role exerted by Gal-3 in many different clinical conditions, Gal-3 is emerging as a new diagnostic, prognostic biomarker and as a new promising therapeutic target. The current review aims to extensively examine the studies published so far on the role of Gal-3 in all the clinical conditions and diseases, listed in alphabetical order, where it was analyzed.

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“…Since side effects of radiation can include induced inflammation and tissue damage, Gal-3 also plays a pivotal role in tissue remodeling and fibrosis. Recently, extensive data on MCP blockade of Gal-3 and reduction of fibrosis in multiple organ tissue animal models 21 - 23 lends further support that the combination may help both ameliorate side effects of radiation therapy and enhance the benefits in a clinical situation.…”

Section: Discussionmentioning

confidence: 97%

Modified Citrus Pectin as a Potential Sensitizer for Radiotherapy in Prostate Cancer

et al. 2018

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Background: Radiotherapy is one of the primary therapies for localized prostatic carcinoma. Therefore, there is an emerging need to sensitize prostatic cancer cells to chemotherapy/radiotherapy. Modified citrus pectin (MCP) is an effective inhibitor of galectin-3 (Gal-3), which is correlated with tumor progression, proliferation, angiogenesis, and apoptosis. Purpose: This study was directed to evaluate the efficacy of combining ionizing radiation (IR) with MCP on PCa cells. Study Design: Effects of treatments on PCa cells survival were evaluated using XTT assay, flow cytometry, and clonogenic survival assay. Expression of selected proteins was estimated using western blotting. Cell motility, migration, and invasion were determined. Contribution of reactive oxygen species production to treatment effects on cell viability was tested. Results: Radiotherapy combined with MCP reduced viability and enhanced radiosensitivity associated with a decrease in Gal-3, cleavage of the precursor of caspase-3, increased expression of the pro-apoptotic protein Bax, and downregulation of DNA repair pathways, poly-ADP-ribose polymerase, and proliferating cell nuclear antigen. MCP significantly reduced the invasive and migratory potential of PCa cells. Combining sodium pyruvate with MCP and IR mitigated the effect on cell viability. Conclusion: Our findings demonstrated that MCP sensitized PCa cells to IR by downregulating anti-apoptotic Gal-3, modulating DNA repair pathways, and increasing ROS production. For the first time the correlation between MCP, radiotherapy, and Gal-3 for prostatic cancer treatment was found. In addition, MCP reduced the metastatic properties of PCa cells. These findings provide MCP as a radiosensitizing agent to enhance IR cytotoxicity, overcome radioresistance, and reduce clinical IR dose.

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Modified citrus pectin stops progression of liver fibrosis by inhibiting galectin-3 and inducing apoptosis of stellate cells

Cited by 53 publications

References 31 publications

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Galectin-3: One Molecule for an Alphabet of Diseases, from A to Z

Modified Citrus Pectin as a Potential Sensitizer for Radiotherapy in Prostate Cancer

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