Abstract
Recent studies have shown that fusarochromanone (FC101), a mycotoxin, is cytotoxic in a variety of cell lines. However, the molecular mechanism underlying its cytotoxicity remains elusive. Here we found that FC101 induced cell death in COS7 and HEK293 cells in part by activating JNK pathway. This is evidenced by the findings that inhibition of JNK with SP600125 or expression of dominant negative c-Jun partially prevented FC101-induced cell death. Furthermore, we observed that FC101-activated JNK pathway was attributed to induction of reactive oxygen species (ROS). Pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger and antioxidant, suppressed FC101-induced activation of JNK and cell death. Moreover, we noticed that FC101 inhibited the serine/threonine protein phosphatases 2A (PP2A) and 5 (PP5) in the cells, which was abrogated by NAC. Overexpression of PP2A or PP5 partially prevented FC101-induced activation of JNK and cell death. The results indicate that FC101-induced ROS inhibits PP2A and PP5, leading to activation of JNK pathway and consequently resulting in cell death.
Highlights
Fusarochromanone (FC101) is a mycotoxin produced by food-borne fungi such as Fusarium equiseti (F. equiseti) and F. roseum
Our findings suggest that the toxicity of FC101 in humans and animals may be prevented and treated by pharmacological interventions, such as antioxidants and JNK inhibitors
To determine whether FC101-induced cytotoxicity is related to induction of reactive oxygen species (ROS), COS7 and human embryonic kidney 293 cells (HEK293) cells were treated with FC101 (0–5 μM) for 24 h, followed by assays for cell viability and ROS induction
Summary
Fusarochromanone (FC101) is a mycotoxin produced by food-borne fungi such as Fusarium equiseti (F. equiseti) and F. roseum. FC101 has recently been found to inhibit cell proliferation and differentiation as well as induce cell death in lymphocytes, osteoblasts, melanoma cells, breast cancer cells, glioblastoma cells, normal cardiac fibroblasts and kidney cells [11,12,13,14,15,16]. Despite these findings, how FC101 causes cytotoxicity is not well understood
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