Inhibition of protein serine/threonine phosphatases by fumonisin B1, a mycotoxin.
Fumonisin B1 (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 hepatocarcinogenic in rats, and although the mechanisms involved have not been clarified, the latter is associated with a weak initiating activity. The effects of FB1 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 microM-3000 microM. Among the five PPs examined, PP5 was most sensitive with an IC50 of 80 microM. This concentration is comparable to that estimated to be reached in the rat body by feeding FB1 to obtain hepatic tumors. Inhibition of PP5 could thus play important roles in the toxicity and carcinogenic action of FB1.
Fukuda
H
H
Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan.
Shima
H
H
Vesonder
R F
RF
Tokuda
H
H
Nishino
H
H
Katoh
S
S
Tamura
S
S
Sugimura
T
T
Nagao
M
M
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000633:toxicity*; D004926:Escherichia coli / Q000235:genetics; D004988:Ethers, Cyclic / Q000633:toxicity; D037341:Fumonisins; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009183:Mycotoxins / Q000633:toxicity*; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000145:classification / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics
D002273:Carcinogens; D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D037341:Fumonisins; D009183:Mycotoxins; D011994:Recombinant Proteins; D019319:Okadaic Acid; C056933:fumonisin B1; D010749:Phosphoprotein Phosphatases