Anti-Thrombin, Anti-Adhesive, Anti-Migratory, and Anti-Proliferative Activities of Sulfated Galactans from the Tropical Green Seaweed, Udotea flabellum.

Maxsuell Mendes Marques,Daniel Bellan,Leandro Costa,Monica Amorim,Hugo Rocha,Rony Viana,Mariana Costa,Edvaldo Trindade,Fernando Presa,Monique Alves

doi:10.3390/md17010005

Abstract

In this study, sulfated polysaccharide-rich extracts were isolated from 22 tropical seaweeds (4 red, 11 brown, and 7 green) found in northeastern Brazil, and evaluated for the role of anticoagulant agents. Fifteen of the extracts showed anticoagulant activity, including all the extracts from green seaweeds. Udotea flabellum (a green seaweed) extract was the most potent, requiring an amount of only 3 µg to double the plasma coagulation time in the activated partial thromboplastin time test. A similar result was obtained with 1 µg of heparin. Two sulfated homogalactans with anticoagulant activity, F-I (130 kDa) and F-II (75 kDa), were isolated from this extract using several bio-guided purification steps. Their anticoagulant activity, as well as properties related to antitumor activity (anti-proliferative, anti-adhesive, and anti-migratory), were accessed. Their anticoagulant activities were close to that of heparin. We found that F-I and F-II (0.5–10 μg/mL) were not able to directly inhibit thrombin. In the presence of anti-thrombin, F-I (0.5 μg/mL) was more effective than heparin (0.5 μg/mL) in inhibiting thrombin, while F-II showed similar effects as heparin. F-I and F-II also inhibited B16-F10 (murine melanoma cells) adhesion, migration, and proliferation on a fibronectin-coated surface, but not on laminin- or collagen I-coated surfaces. Except for the antiproliferative activity, the other effects of F-I and F-II were eliminated upon their desulfation (~50%), indicating that the degree of sulfation is not as important for F-I and F-II anti-proliferative activity as the sulfation position. Taken together, the results provide strong evidence for the potential utility of sulfated galactans from U. flabellum, making these compounds an interesting option for future investigations that aim to design new anticoagulant/antitumor agents.

Highlights

Cancer is a broad term used to represent a class of over 100 different types of diseases that share specific features, including disordered proliferation of abnormal cells with invasive potential.Trachea, bronchus, lung, colon, rectum and breast cancers were some of the leading causes of death in the Western world in 2016 [1]
sulfated polysaccharide (SP)-rich extracts were isolated from the tropical seaweeds described in Section 3, and their anticoagulant activities were determined using the activated partial thromboplastin time (APTT)
The results are shown in Table 1; more than 50% of the extracts succeeded in altering the plasma coagulation time

Summary

Introduction

Cancer is a broad term used to represent a class of over 100 different types of diseases that share specific features, including disordered proliferation of abnormal cells with invasive potential. Bronchus, lung, colon, rectum and breast cancers were some of the leading causes of death in the Western world in 2016 [1]. Cancer-associated thrombosis is the second leading cause of death in cancer patients, after death from cancer itself. The risk of a venous thromboembolism is four- to seven-fold higher in patients with cancer than in those without cancer. The clinical presentation of cancer-associated thrombosis includes deep vein thrombosis, pulmonary embolism, chronic disseminated intravascular coagulation associated with non-bacterial thrombotic endocarditis, and arterial thrombosis. Secondary thrombotic events related to chemotherapy or central venous catheterization are included in the description of cancer-associated thrombosis [3]

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Conclusion