In vitro and in vivo anti-primary effusion lymphoma activities of fucoidan extracted from Cladosiphon okamuranus Tokida.

Primary effusion lymphoma (PEL) caused by Kaposi's sarcoma-associated herpesvirus (KSHV) is characterized by lymphomatous effusion in body cavities and poor prognosis. There is still no effective treatment for PEL. Fucoidan, a major sulfated polysaccharide isolated from brown seaweeds, has an attractive array of bioactivities such as cancer inhibition. However, the effects of fucoidan on PEL cells remain unclear. We investigated the anti-PEL effects of fucoidan obtained from Cladosiphon okamuranus Tokida cultivated in Okinawa. Fucoidan dose-dependently inhibited the proliferation of KSHV-infected PEL cell lines, and provoked G1 cell cycle arrest, which was accompanied by CDK4 and CDK6 downregulation. Fucoidan also induced apoptosis of PEL cells through caspase-3, -8 and -9 activation; this occurred partly through the downregulation of anti-apoptotic Bcl-xL, Mcl-1 and XIAP proteins. Fucoidan also suppressed nuclear factor-κB, activator protein-1 (AP-1), and T-lymphokine-activated killer cell-originated protein kinase (TOPK) signaling pathways through inhibition of phosphorylation of IκBα and TOPK, and the expression of AP-1 family proteins, JunB and JunD. Oral administration of fucoidan effectively inhibited the development of PEL cells and ascites in a xenograft SCID mouse model, with minimal serious adverse effects. Notably, native fucoidan exhibited a more efficient anti-PEL effect than nanoparticle fucoidan. These preclinical findings highlight the anti-PEL actions of fucoidan, suggesting it could be potentially useful for the prevention and treatment of PEL.