Allylic structures in cancer drugs and body metabolites that control cell life and death.

This review presents data supporting the hypothesis that the anticancer activity of ceramide and many antineoplastic drugs is due to a 3-carbon allylic moiety (-C = C-C-) containing oxygen or nitrogen. The polar atom appears as an alcohol, ether, ester, amide, ketone, amine or imino group. Some drugs lack the allylic moiety, but metabolic oxidation or oxygenation in patients introduces the moiety. The allylic compounds kill cancer cells by: i) interference with ubiquinone in mitochondria, generating reactive oxygen species (ROS); ii) activation of enzymatic hydrolysis of sphingomyelin by the ROS, forming ceramide, which initiates mitochondrial destruction and apoptosis; iii) activation of the phosphorylation and dephosphorylation of proteins involved in apoptosis by ceramide and some allylic drugs and iv) activation of certain proteases, such as cathepsin D, by ceramide.