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

Marine seaweeds are a rich source of sulfated polysaccharides (SPs) 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 SPs 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 SPs profile on murine MΦs (RAW 264.7 cells). The direct SPs 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 SPs. The three SPs 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 a macrophage M1 phenotype, which in turn releases a factor that inhibits B16-F10 proliferation.