Abstract 4566: Fusarochromanone inhibits cell proliferation and induces cell death in COS7 cells

Abstract

Abstract Fusarochromanone (FC101) is a mycotoxin produced by Fusarium equiseti. Contamination of FC101 occurs frequently in grains and feedstuffs, which has been found to cause tibial dyschondroplasia in chickens and Kashin-Beck disease in children. However, little is known about the toxicity of FC101 in the kidney. In this study, we found that FC101 inhibited cell proliferation and induced cell death in monkey kidney fibroblasts (COS7) in a concentration-dependent manner. Furthermore, we found that FC101 inhibited cell proliferation by arresting cells in G1 phase of the cell cycle, which was associated with reduced expression of CDK4, cyclin D1, and Cdc25A, as well as decreased phosphorylation of Rb. FC101 induced cell death by downregulating expression of Bcl-2, Bcl-xl and survivin, and upregulating expression of Bad, leading to increased cleavages of caspase 3 and PARP. Also, FC101 induced translocation of apoptosis inducing factor (AIF) from the cytosol to the nucleus. Furthermore, FC101 activation of JNK cascade also contributed to cell death, as inhibition of JNK with SP600125 or expression of dominant negative c-Jun attenuated FC101-induced cell death. In addition, we observed that FC101-induced cell death linked to induction of reactive oxygen species (ROS) in the cells, since addition of antioxidants (co-enzyme Q10 and N-acetyl-cysteine) attenuated the toxic effect of FC101 on the cells. Our findings suggest that FC101 may exert its toxicity in COS7 cells through oxidative stress. Citation Format: Ying Gu, Shanxiang Jiang, Elahe Mahdavian, Shile Huang. Fusarochromanone inhibits cell proliferation and induces cell death in COS7 cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4566. doi:10.1158/1538-7445.AM2014-4566