A new promising anticancer agent: A glycosaminoglycan-mimetic derived from the marine bacterial infernan...

Marine microorganisms are a promising source of innovative compounds for medical applications. The present study aimed to investigate anticancer potential of oversulfated low molecular weight derivatives, named OSIDs, prepared from infernan, a marine bacterial exopolysaccharide. In order to identify a lead, OSIDs with different sulfate contents and molecular weights were firstly evaluated in vitro in a large series of human and murine tumor cell lines. Among all derivatives tested, OSID4 was the most effective, showing a significant dose-dependent inhibitory effect on the viability of cancer cells. OSID4 was then able to significantly slow down progression of lung and melanoma tumor growth in immunocompetent tumor-bearing mouse models. In immunodeficient mice bearing a human lung carcinoma, a notable inhibitory effect of OSID4, comparable to doxorubicin, was observed. In combination with doxorubicin, OSID4 did not exhibit any drug interaction. The activity of OSID4 was confirmed by its modulatory effect on the transcriptomic profile of human lung cancer cells. Finally, toxicity and pharmacokinetic parameters disclosed that OSID4 presented no toxicity and no bleeding risk. In conclusion, by combining its notable anticancer and moderate anticoagulant activities, OSID4 may be promising for treatment of cancers associated with a high risk of thromboembolic events.