Apoptosis Inducement by Plant and Fungus Sphingoid Bases in Human Colon Cancer Cells

Abstract

In the present study, examination was made of the apoptosis-inducing activity of sphingoid bases from plant and fungus sphingolipids and the mechanisms involved. Sphingoid bases from maize and lactic yeast, Kluyveromyces lactis (trans-4, trans-8-sphingadienine, trans-4, cis-8-sphingadienine and 9-methyl-trans-4, trans-8-sphingadienine) were found to bring about apoptosis in Caco-2 human colon cancer cells. The apoptosis-inducing activity of trans-4, cis-8-sphingadienine and 9-methyl-trans-4, trans-8-sphingadienine was significantly higher than that of trans-4-sphingenine. In differentiated Caco-2 cells, the model for normal intestine cells, no apoptosis by sphingoid bases was noted to occur. The Caspase-3 inhibitor suppressed sphingoid base-induced apoptosis in Caco-2 cells, thus indicating activation of the caspase pathway to be related to sphingoid base-induced apoptosis in Caco-2 cells. Sphingoid bases from plants and fungi caused intracellular β-catenin content to decrease, as was also noted in the case of sphingosine and sphinganine from animal tissues. It would thus appear that sphingolipids in edible plants and fungi may be considered functional lipids and the apoptosis-inducing pathway by sphingoid bases may be related to signal transduction via β-catenin.