Natural substances are strategic candidates for drug development in cancer research. Marine-derived molecules are of special interest due to their wide range of biological activities and sustainable large-scale production. Melanoma is a type of skin cancer that originates from genetic mutations in melanocytes. BRAF, RAS, and NF1 mutations are described as the major melanoma drivers, but approximately 20% of patients lack these mutations and are included in the triple wild-type (tripleWT) classification. Recent advances in targeted therapy directed at driver mutations along with immunotherapy have only partially improved patients’ overall survival, and consequently, melanoma remains deadly when in advanced stages. Fucose-containing sulfated polysaccharides (FCSP) are potential candidates to treat melanoma; therefore, we investigated Fucan A, a FCSP from Spatoglossum schröederi brown seaweed, in vitro in human melanoma cell lines presenting different mutations. Up to 72 h Fucan A treatment was not cytotoxic either to normal melanocytes or melanoma cell lines. Interestingly, it was able to impair the tripleWT CHL-1 cell proliferation (57%), comparable to the chemotherapeutic cytotoxic drug cisplatin results, with the advantage of not causing cytotoxicity. Fucan A increased CHL-1 doubling time, an effect attributed to cell cycle arrest. Vascular mimicry, a close related angiogenesis process, was also impaired (73%). Fucan A mode of action could be related to gene expression modulation, in special β-catenin downregulation, a molecule with protagonist roles in important signaling pathways. Taken together, results indicate that Fucan A is a potential anticancer molecule and, therefore, deserves further investigation.

天然物质是癌症研究中药物开发的战略候选者。海洋衍生分子因其广泛的生物活性和可持续的大规模生产而受到特别关注。黑色素瘤是一种皮肤癌，起源于黑色素细胞的基因突变。BRAF、RAS和NF1突变被描述为主要的黑色素瘤驱动因素，但大约 20% 的患者缺乏这些突变，并包含在三重野生型 (tripleWT) 分类中。针对驱动突变的靶向治疗和免疫疗法的最新进展仅部分改善了患者的总体生存率，因此，黑色素瘤在晚期仍然是致命的。含岩藻糖的硫酸多糖（FCSP）是治疗黑色素瘤的潜在候选者；因此，我们在体外对呈现不同突变的人类黑色素瘤细胞系进行了 Fucan A （一种来自Spatoglossum schröederi棕色海藻的 FCSP）的研究。长达 72 小时的 Fucan A 处理对正常黑色素细胞或黑色素瘤细胞系都没有细胞毒性。有趣的是，它能够损害 TripleWT CHL-1 细胞增殖 (57%)，与化疗细胞毒性药物顺铂的结果相当，且具有不引起细胞毒性的优点。Fucan A 增加了 CHL-1 倍增时间，这是细胞周期停滞的效应。血管拟态，一种密切相关的血管生成过程，也受到损害（73%）。Fucan A 的作用模式可能与基因表达调节有关，特别是 β-catenin 下调，β-catenin 是一种在重要信号传导途径中发挥主角作用的分子。综上所述，结果表明 Fucan A 是一种潜在的抗癌分子，因此值得进一步研究。