Non-cytotoxic sulfated agaran from red seaweed Gracilaria cornea induces antitumor phenotype on macrophages in vitro and inhibits tumor growth in vivo

Abstract

Marine seaweeds are a rich source of sulfated polysaccharides with several biological effects, including antitumor. Some polysaccharides activate macrophages (Mfs) to an antitumor phenotype. In this study, we evaluate whether sulfated galactans (SGs), isolated from red seaweeds Gracilaria cornea (SG-Gc) and Solieria filiformis (SG-Sf), could activate a murine Mfs (RAW 264.7) to an antitumor phenotype. Additionally, we assessed their potential antitumor effects. Both SGs induced nitric oxide release by Mfs. SG-Sf inhibited a murine metastatic melanoma cell line (B16-F10) proliferation compared with the negative control, but SG-Gc did not inhibit B16-F10 proliferation. Notably, a conditioned medium from RAW 264.7 incubated with SG-Gc and SG-Sf inhibited B16-F10 proliferation. Since there was no direct cytotoxicity against B16-F10, we selected SG-Gc for further assays. S SG-Gc induced TNF-α release and increase of the M1 markers iNOS, MHCII, and CD86. Furthermore, 25 mg/kg SG-Gc administered intraperitoneally in B16-F10 melanoma-bearing mice inhibited tumor growth by 60% compared to negative control. In addition, SG-Gc promoted the immunostimulant effect observed on the spleen. No toxic effects were observed in mice treated with SG-Gc. In summary, we identified SG-Gc as an immunomodulatory and antitumor agent.