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Although recent advances in targeted and immunotherapy, metastatic melanoma treatment still poses as a challenge, with limited success and a variety of severe adverse effects. Polysaccharides from natural sources have been explored as a new approach to tackle cancer and melanoma treatment limitations, even reaching clinical trials. One prominent group of biological active polysaccharides are fucoidans - sulfated polysaccharides mainly constituted of fucose and obtained from brown seaweed. In the present study, we explored the antimelanoma activities of Fucan A, a highly sulfated fucoidan obtained from Spatoglossum schröederi. Fucan A presented a selective antiproliferative effect against murine melanoma B16-F10 cell line impacting cell cycle progression in concentrations of 100 and 1000 μg⸱mL−1 while also reducing its colony formation and invasive capacity, as well as modulating invasion mechanistically related genes - namely MMP-9, MMP-14, glypican-3 and perlecan. Fucan A also reduced in vivo solid tumor volume in a daily post-cell inoculation treatment regimen with a 100 mg⸱Kg−1 dosage. Additionally, using a 48 h pre-treatment regimen in a reduced dosage (30 mg⸱Kg−1), Fucan A reduced pulmonary metastasis colonization, with limited to non-detectable adverse effects. These results associated with the explorable commercial potential of S. schröederi indicate an interesting compound to be further explored as a possible antimelanoma drug. • Fucan A from Spatoglossum schröederi impairs melanoma traits. • Fucan A presented a selective antiproliferative and reduced B16-F10 invasion. • In vivo treatment with Fucan A reduced B16-F10 tumor volume and metastasis. • Fucan A treated animals presented limited to non-detectable adverse effects. [ABSTRACT FROM AUTHOR]

• A sulfated homogalactan from Codium isthmocladum presents promising in vitro and in vivo activities in murine melanoma models. • 3G4S does not induce cell cytotoxicity nor cell proliferation changes in B16-F10 cell line. • In vivo treatment with 3G4S resulted in solid tumor and experimental metastasis model development reduction without exerting detectable side effects in mice. Melanoma is the most lethal form of skin cancer, with a worldwide increase in incidence. Despite the increased overall survival of metastatic melanoma patients given recent advances in targeted and immunotherapy, it still has a poor prognosis and available treatment options carry diverse severe side effects. Polysaccharides from seaweed have been shown to exert antitumor activities. Here we show in vitro and in vivo antitumor activities of a sulfated homogalactan (named 3G4S) from Codium isthmocladum seaweed in the B16-F10 murine melanoma cell line. 3G4S did not induce cytotoxicity or proliferation changes; however, it was able to reduce solid tumor growth and metastasis, while not inducing side effects in mice. B16-F10 cells traits related to the metastatic cascade were also impaired by 3G4S, reducing cell invasion, colony-forming capacity and membrane glycoconjugates. Therefore, 3G4S shows promising antitumor activities without the commonly associated drawbacks of cancer treatments and can be further explored. [ABSTRACT FROM AUTHOR]