The mycotoxin fumonisin B1 inhibits integrin-mediated cell-matrix adhesion

Fumonisin B1 (FB1), a mycotoxin produced by the corn fungus Fusarium monili forme, causes a variety of animal diseases and is a suspected human carcino gen. The FB1 molecule bears remarkable structural resemblance to the long-c hain sphingoid base backbones of sphingolipids. The toxicity and carcinogen icity of FB1 has been ascribed to its ability to inhibit ceramide synthase, a key enzyme in the metabolism of complex sphingolipids. In this study we have investigated whether the exposure of B16-BL6 mouse melanoma cells to F B1 affects cell growth and integrin-mediated cell matrix adhesion. Cell tre atment with the highest tested dose (75 mu M) of FB1 for 72 h induced an ab out 20% inhibition of cell growth. FBI strongly affected B16-BL6 cell adhes ion to immobilized fibronectin, by causing a dose-dependent inhibition of c ell attachment to this substrate. FB1 also inhibited in a dose-dependent ma nner the adhesion of B16-BL6 cells to the immobilized anti-fibronectin rece ptor antibody, whereas it affected only to a low extent cell attachment to concanavalin A. Our results demonstrate that FB1 treatment alters integrin adhesive activity, thus affecting all cellular integrin-dependent functions . (C) 1999 Societe francaise de biochimie et biologie moleculaire / Edition s scientifiques et medicales Elsevier SAS.