Induction of Apoptosis by Fumonisin B1in HT29 Cells Is Mediated by the Accumulation of Endogenous Free Sphingoid Bases

Abstract

Fumonisin B1(FB1) and aminopentol (AP1) (which is formed by hydrolysis of FB1) are found in corn contaminated with some strains ofFusarium moniliforme.Incubation of HT29 cells (a human colonic cell line) with FB1or AP1caused a significant reduction in cell number; AP1was less potent, with 50 μM AP1causing the same reduction (ca. 30% after 24 h) as 10 μM FB1. The reduction in cell number reflected increases in DNA fragmentation and the percentage of apoptotic cells. Both FB1and AP1caused the accumulation of sphinganine (25- and 35-fold by 10 μM FB1and 50 μM AP1, respectively); thus, concentrations of FB1and AP1that caused comparable reductions in cell number were also similar with respect to elevation of sphinganine, a compound that is growth inhibitory and cytotoxic. Inhibition of the first step of sphingolipid biosynthesis with ISP-1 prevented the elevation in sphinganine, DNA fragmentation, and apoptosis induced by FB1. Therefore, these effects of FB1on HT29 cells can be attributed to the accumulation of sphinganine. Since consumption of food contaminated withFusarium moniliforme(Sheldon) exposes colonic cells to these mycotoxins, the possibility that FB1and AP1are toxic for intestinal cellsin vivoshould be evaluated, especially in the light of the recent report (Bhatet al., Clin. Toxicol.35, 249, 1997) describing intestinal disturbances in humans after consumption of moldy corn and sorghum containing fumonisins.