Inhibition of protein serine threonine phosphatases by fumonisin B-1, a mycotoxin

Fumonisin B-1 (FB1), a mycotoxin produced by the fungus Fusarium moniliforme, which is a common contaminant of corn, is suspected to be a cause of human esophageal cancer. FB1 is hepatotoxic and hepato-carcinogenic in rats, and although the mechanisms involved have not been clarified, the latter is associated with a weak initiating activity. The effects of FB, on the activity of protein serine/threonine phosphatases (PPs) (PP1, PP2A, PP2B, PP2C and PP5/T/K/H) were investigated in the present study. Inhibition of dephosphorylation was noted for all five PPs with IC50 values of 80 mu M-3000 mu M. Among the five PPs examined, PP5 was most sensitive with an IC50 of 80 mu M. This concentration is comparable to that estimated to be reached in the rat body by feeding FB, to obtain hepatic tumors. Inhibition of PP5 could thus play important roles in the toxicity and carcinogenic action of FB1. (C) 1996 Academic Press, Inc.