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The Key Role of Sulfation and Branching on Fucoidan Antitumor Activity
Catarina Oliveira1,2, Andreia S Ferreira3, Ramon Novoa-Carballal1,2
13B's Research Group-Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, 4805-017, Barco, Guimarães, Portugal.
Abstract:
There is an urgent need for antitumor bioactive agents with minimal or no side effects over normal adjacent cells. Fucoidan is a marine-origin polymer with known antitumor activity. However, there are still some concerns about its application due to the inconsistent experimental results, specifically its toxicity over normal cells and the mechanism behind its action. Herein, three fucoidan extracts (FEs) have been tested over normal and breast cancer cell lines. From cytotoxicity results, only one of the extracts shows selective antitumor behavior (at 0.2 mg mL-1 ), despite similarities in sulfation degree and carbohydrates composition. Although the three FEs present different molecular weights, depolymerization of selected samples discarded Mw as the key factor in the antitumor activity. Significant differences in sulfates position and branching are observed, presenting FE 2 the higher branching degree. Based on all these experimental data, it is believed that these last two properties are the ones that influence the cytotoxic effects of fucoidan extracts.
Insights
Marine fucoidan extracts show potential as antitumor agents. Structural differences, specifically sulfate positioning and branching, influence their selective anticancer activity and toxicity to normal cells.
Area of Science:
- Marine Biotechnology
- Biochemistry
- Cancer Biology
Background:
- There is a critical need for effective antitumor agents with minimal side effects on healthy cells.
- Fucoidan, a marine polymer, exhibits known antitumor properties, but its clinical application is hindered by variable efficacy and toxicity.
- Understanding the structural basis of fucoidan's bioactivity is essential for optimizing its therapeutic potential.
Purpose of the Study:
- To investigate the selective antitumor activity of three distinct fucoidan extracts (FEs) against breast cancer cell lines.
- To identify the specific structural characteristics of fucoidan responsible for its cytotoxic effects on cancer cells versus normal cells.
- To elucidate the mechanism underlying fucoidan's antitumor action, focusing on molecular weight, sulfation, and branching.
Main Methods:
- Cytotoxicity assays were performed on normal and breast cancer cell lines using three different fucoidan extracts.
- Molecular weight analysis and depolymerization were conducted to assess the role of molecular size.
- Analysis of sulfation degree, sulfate positioning, and carbohydrate branching was carried out to determine structural variations.
Main Results:
- One of the three fucoidan extracts demonstrated selective antitumor activity against cancer cells at a concentration of 0.2 mg/mL.
- Molecular weight was not identified as the primary determinant of antitumor activity, as depolymerization studies yielded inconclusive results.
- Significant variations in sulfate positioning and branching patterns were observed among the fucoidan extracts, with FE 2 exhibiting higher branching.
Conclusions:
- Fucoidan extracts possess selective antitumor potential, but their efficacy varies significantly based on structural characteristics.
- Sulfate positioning and branching degree, rather than molecular weight, are likely the key factors influencing fucoidan's cytotoxic effects.
- Further research into fucoidan structure-activity relationships is warranted to develop optimized marine-derived anticancer therapies.
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