Sterigmatocystin induced cytotoxicity and disturbed lipid metabolism

Abstract

Sterigmatocystin (STC), as a mycotoxin, widely exists the environment and food, and threatens the health of animals and human. Since STC has carcinogenicity and cancer is closely related to dysregulation in lipid metabolism, it is necessary to identify the effect of STC on lipid metabolism in vitro. In this research, the cytotoxicity of STC on HL-7702 cells were evaluated, analyzed by cell viability, reactive oxygen species (ROS) levels and relative genes transcription levels. Meanwhile, lipid changes were measured by oil red O staining. Further, HPLC-MS-based untargeted lipidomics were exploited to determine the alteration in endogenous lipid metabolites when exposed to STC. The results showed that the treatment of STC decreased cell viability, increased ROS levels, triggered abnormal cell cycle-related genes expression and induced apoptosis. Besides, STC exposure resulted in abnormal accumulation of lipid droplets. Lipidomics analysis further revealed that STC induced abnormal lipids metabolism, including lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), ceramides (Cer), cholesterol ester (ChE), fatty acid (FA), triglyceride (TG) and acyl carnitine (AcCa). Meanwhile, lipid species of LPC (16:0), LPC (16:1), LPC (18:0), LPC (18:1), LPC (18:2), LPE (16:0), and FA (20:4) are significantly decreased, but TG (16:0/16:1/16:1) and TG (18:1/18:1/18:2) increased dramatically. To sum up, these findings provided fresh insights to explore cytotoxic mechanism of STC.