Concentration-dependent effect of fumonisin B₁ on apoptosis in oesophageal cancer cells

The geographical distribution of oesophageal cancer is linked to the exposure of fumonisin B₁ (FB₁), a mycotoxin produced by fungi that contaminates staple food worldwide. Non-genotoxic carcinogens like FB₁ disturb homeostasis through increased cell proliferation or suppression of apoptosis. This study investigated the involvement of FB₁ (0-20 μM) in spindle-shaped N-cadherin (+) CD45 (-) osteoblastic (SNO) cell death. Cell viability and death were assessed using the MTS and Annexin V-Fluos assays, respectively. Caspase activities were determined luminometrically and the comet assay assessed DNA damage. Induction of oxoguanine glycosylase 1 (OGG1) was measured using quantitative Polymerase Chain Reaction (qPCR), while cleaved poly (ADP-ribose) polymerase 1 (PARP-1) and Bax were determined by western blotting. Cell viability and PARP-1 cleavage were not affected by 1.25 μM FB₁, but phosphatidylserine externalization, Bax protein expression, caspase activity, comet tail length and OGG1 transcripts were increased. The reduced cell viability in 10 μM FB₁-treated cells was accompanied by corresponding increases in externalized phosphatidylserine, Bax, caspase-3/7 activity and cleaved PARP-1. The OGG1 transcripts were not significantly increased, but comet tails were increased. Bax, caspase-3/7 activities and cleaved PARP-1 were inhibited at 20 μM FB₁. In addition, the OGG1 transcript levels were decreased ( p < 0.0001) along with comet lengths ( p < 0.0001). This study showed that FB₁-induced apoptosis in SNO cells may be caspase-dependent or caspase-independent; the pathway used depends on the exposure concentration.