Targeting ceramide by dietary means to stimulate apoptosis in tumor cells

The objective of this review is to summarize present knowledge concerning specific dietary components that increase intracellular ceramide and that promote apoptosis in tumor cells. The production of ceramide and the initiation of apoptosis or programmed cell death in tumor cells in response to nutraceuticals or dietary factors may offer a model to understand how specific dietary components offer protection from select cancers. The review summarizes the central role that ceramide plays in sphingolipid metabolism and the experimental evidence that ceramide induces apoptosis in tumor cells. The review identifies several isolated nutrients and dietary supplements that increase ceramide production in tumor cells both in vitro and in some cases in vivo. These dietary components include the phytosterol β-sitosterol, the fat-soluble vitamins vitamin A and vitamin D, sphingolipids, and some select fatty acids including palmitic acid. The formation of ceramide in tumor cells by these dietary components is reviewed and shown to be either from de novo ceramide synthesis or from the stimulated action of sphingomyelinases on membrane sphingomyelin. The review concludes that the consumption of specific nutraceuticals either individually or in combination may provide a nontoxic means to protect humans from several types of common cancers.