INHIBITION OF PROTEIN SERINE/THREONINE PHOSPHATASES BY FUMONISIN B1

Authors: Vesonder, Ronald; FUKUDA, HIROKAZU - NATL CANCER INST, JAPAN; SHIMA, HIROSHI - NATL CANCER INST, JAPAN; TOKUDA, HARUKUNI - KYOTO PREF UNIV, JAPAN; NISHINO, HOYOKU - KYOTO PREF UNIV, JAPAN; KATOH, SEISHI - SAGAMI CHEM CTR, JAPAN; TAMURA, SHINRI - INST DEV CANCER, JAPAN; SUGIMURA, TAKASHI - NATL CANCER INST, JAPAN; NAGAO, MINAKO - NATL CANCER INST, JAPAN

Submitted to: American Society of Pharmacognosy
Publication Type: Abstract Only
Publication Acceptance Date: 7/31/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: The fumonisins are cosmopolitan mycotoxins produced by Fusarium moniliforme commonly found on corn. We reported some similarities between fumonisin B1 (FB1) and okadic acid; both are tumor promoters in two-stage carcinogenesis in mouse skin initiated with a single application of 7,12-dimethylbenzanthracene. Both are negative for induction of Epstein-Barr virus early antigen and activation of protein kinase C, thereby differing from the typical tumor promoter, 12-O-tetradecanoyl phorobol acetate. Here we report on the effects of FB1 a non-genotoxic and nonmutagenic hepatocarcinogen, on the activity of protein serine/threonine phosphatases (PPs) (subunits PP2A, PP2B, PP2C, and PP5/T/K/H). Inhibitions of dephosphorylation were noted for all the PPs (IC50 values of 80-3000 uM). The PP5 was the most sensitive; an IC50 of 80 uM. This is a comparable concentration to that in rats fed FB1 that exhibit hepatic tumors. A current idea is that FB1 acts on the subunit PP5 to alter the function of the phosphatase in the subcellular signal transduction pathway, thus predisposing the cell to tumor initiation. Since fumonisins are found in corn, a staple in human and animal food in the USA, the inhibition of PP5 could play an important role in toxicity and in carcinogenic action of FB1.