A study on the targeting of ceramide metabolism by (-)-epicatechin gallate, catechin and quercetin in A-549 lung cancer cell line

Catechin, epicatechin gallate (ECG) and quercetin, as bioactive flavonoids, have been shown to possess anticarcinogenic effects. Ceramide plays an important role in killing tumor cells. Accordingly, the aim of this study was to clarify the involvement of these compounds in ceramide metabolism in A549 cancerous cell line. Spectrophotometer, cell culture and HPLC methods were used. Cell viability index showed different potential of cytotoxicity effect for each of the studied agents, among which ECG was more potent. This index decreased significantly over 100 to 250 micro;M concentrations of treatment with respect to control. Cell treatments also caused considerable increase in ceramide level within cells in a dosedependent manner. Sphingomyelinase activity increased significantly in treatment with quercetin and catechin. There was significant inhibition in acid ceramidase activity of cell extract in response to each of the three compounds, particularly over 100 micro;M in comparison with control. Data also showed no significant variation in glycosyl ceramide synthase activity in treated cells with quercetin, whereas the activity decreased significantly by Catechin and/or ECG. It is our conviction that different effects on ceramide metabolism enzymes may be related to various chemical groups on the common structure of the studied compounds. Due to structurefunction relationship, these compounds had different effects on ceramide generation. Elevation in ceramide content in A549 cancer cell line induced apoptosis, which led to anticancerous effects, as observed in this study.