A Fucose-Containing Sulfated Polysaccharide from Spatoglossum schröederi Potentially Targets Tumor Growth Rather Than Cytotoxicity: Distinguishing Action on Human Melanoma Cell Lines.

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 ß-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.

Polybrominated diphenyl ethers BDE-47 and BDE-99 modulate murine melanoma cell phenotype in vitro.

Cancer is one of the leading causes of mortality worldwide. Even with the advances of pharmaceutical industry and treatments, the mortality rate for various types of cancer remains high. In particular, phenotypic alterations of tumor cells concerning drug efflux, migratory and invasive capabilities may represent a hurdle for cancer treatment and contribute to poor prognosis. In the present study, we investigated the effects of polybrominated diphenyl ethers (PBDEs) used as flame retardants on phenotypic features of melanoma cells that are important for cancer. Murine melanoma B16-F1 (less metastatic) and B16-F10 (more metastatic) cells were exposed to 0.01-1.0 nM of BDE-47 (2,2',4,4'-tetrabromodiphenyl ether), BDE-99 (2,2',4,4',5-pentabromodiphenyl ether), and the mixture of both (at 0.01 nM) for 24 h (acute exposure) and 15 days (chronic exposure). The polybrominated diphenyl ethers (PBDEs) did not affect cell viability but led to increased drug efflux transporter activity, cell migration, and colony formation, as well as overexpression of Abcc2 (ATP-binding cassette subfamily C member 2), Mmp-2 (matrix metalloproteinase-2), Mmp-9 (matrix metalloproteinase-9), and Tp53 (tumor protein p53) genes and downregulation of Timp-3 (tissue inhibitor of metalloproteinase 3) gene in B16-F10 cells. These effects are consistent with increased aggressiveness and malignancy of tumors due to exposure to the flame retardants and raise some concerns on the effects such chemicals may have on melanoma treatment and cancer prognosis.