Investigation of quinocetone-induced mitochondrial damage and apoptosis in HepG2 cells and compared with its metabolites

Abstract

Quinocetone (QCT) has been widely used as an animal growth promoter in China. However, amounts of available data indicated that QCT probably had potential toxicity. The present study was aimed to investigate the genotoxicity, mitochondrial damage and apoptosis in HepG2 cells for QCT and its metabolites, DQCT and MQCA. QCT has seriously cytotoxic to HepG2 cells. The cell viability test and cytokinesis-block micronucleus test showed that the micronucleus frequency of cells treated with QCT has increased significantly, compared with DQCT and MQCA. With increasing of QCT concentrations, the genomic template stability and mitochondrial damage of HepG2 cells were aggravated. QCT-induced apoptosis in HepG2 cells were also observed. Data of caspase activities in measurement and real-time RT-PCR possibly suggested both of the mitochondria-dependent and mitochondria-independent pathways participated in the HepG2 cells apoptosis. However, all the results suggested that DQCT and MQCA showed only a little cytotoxic to HepG2 cells. In a word, QCT had toxic effects on HepG2 cells and resulted in the mitochondria-dependent and mitochondria-independent pathways of apoptosis, but the intermediate metabolites of QCT (DQCT and MQCA) were not.

Keywords: 1,4-Bisdesoxyquinocetone; 3-Methylquinoxaline-2-carboxylic acid; Apoptosis; Genotoxicity; Mitochondrial damage; Quinocetone.