Sulfated agarans from red seaweed Gracilaria cornea induce macrophages polarization to an antitumor M1 phenotype

Marine seaweeds are a rich source of sulfated polysaccharides with several biological activities, including antitumor effect. Some polysaccharides are also described to activate macrophages (Mϕs) to an antitumor M1-like phenotype. Here, we evaluated the capacity of sulfated galactans (SGs) extracts obtained from three seaweed species, Gracilaria cornea (Gc-E), Gracilaria birdiae (Gb-E), and Solieria filiformis (Sf-E), to activate the Mϕs antitumor M1 phenotype. The nitric oxide production, MHCII, and CD86 (M1 markers) were evaluated to screening the bioactive SGs profile on murine Mϕs (RAW 264.7 cells). The direct SGs antiproliferative effect was tested on melanoma B16-F10 cells. In another experimental setting, B16-F10 cells were incubated with a conditioned medium obtained from Mϕs exposed to SGs. The three SGs tested induced NO release. Sf-E directly inhibited B16-F10 cells proliferation compared with the saline group, but Gc-E and Gb-E failed to inhibit cell proliferation. Notably, a conditioned medium (CM) of Mϕs incubated with Gc-E and Sf-E, but not of Gb-E, inhibited the proliferation of B16-F10 cells. Gc-E also induced TNF-α release and increase of M1 markers such as iNOS, MHCII, and CD86. Therefore, Gc-E activates Mϕs to M1 phenotype, which in turn releases a factor that inhibits B16-F10 proliferation. ### Competing Interest Statement The authors have declared no competing interest.