Quercetin Affects Ceramide but not Sphingosine-1-phosphate in ras-transformed 3T3 Fibroblasts

Abstract

Investigations were carried out on the effect of quercetin on the level of the major sphingolipid metabolites in ras-transformed 3T3 fibroblasts. Quercetin is a polyphenol of a significant biomedical importance, which has been reported to show beneficial effects such as antioxidant, anti-neoplastic, anti-ageing, etc. Sphingolipids are functionally active lipid molecules, which regulate important cellular processes, like proliferation, apoptosis and transmembrane signalling, among others. Despite the numerous investigations devoted to the influence of quercetin on the lipid metabolism of various types of cancer cells, the mechanism of this influence on the major sphingolipid pathways still remains unclear. Our studies showed that sphingomyelin was decreased in ras-transformed 3T3 fibroblasts, whereas ceramide, which is a pro-apoptotic factor, was increased as a result of elevated neutral sphingomyelinase activity. However, the level of sphingosine-1-phosphate, which is related to cell proliferation, was not altered as a result of quercetin treatment, which is an unexpected finding when compared to our previous studies with cancer cells. In addition, the observed changes in the balancing enzyme in the sphingolipid pathway, sphingosine kinase 1, which produces sphingosine-1-phosphate, were not statistically significant in quercetin-treated oncogene-transformed fibroblasts. The presented data are useful for better understanding of the effect of flavonoids on the regulation of sphingolipid metabolism and could help in the development of complex antitumour therapeutic approaches, involving natural antitumour agents like polyphenols.