Sulfated polysaccharides 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 (M{phi}s) 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 M{phi}s antitumor M1 phenotype. The nitric oxide production, MHCII, and CD86 (M1 markers) were evaluated to screening the bioactive SGs profile on murine M{phi}s (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 M{phi}s 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 M{phi}s incubated with Gc-E and Sf-E, but not of Gb-E, inhibited the proliferation of B16-F10 cells. Gc-E also induced TNF- release and increase of M1 markers such as iNOS, MHCII, and CD86. Therefore, Gc-E activates M{phi}s to M1 phenotype, which in turn releases a factor that inhibits B16-F10 proliferation.