Betulinic acid is a natural product with a range of biological effects, for example potent antitumor activity. This anticancer property is linked to its ability to induce apoptotic cell death in cancer cells by triggering the mitochondrial pathway of apoptosis. In contrast to the cytotoxicity of betulinic acid against a variety of cancer types, normal cells and tissue are relatively resistant to betulinic acid, pointing to a therapeutic window. Compounds that exert a direct action on mitochondria present promising experimental cancer therapeutics, since they may trigger cell death under circumstances in which standard chemotherapeutics fail. Thus, mitochondrion-targeted agents such as betulinic acid hold great promise as a novel therapeutic strategy in the treatment of human cancers.
Keywords: AIF, apoptosis inducing factor; Apaf-1, Apoptotic protease activating factor-1; BA, betulinic acid; DIABLO, direct IAP Binding protein with Low PI; HtrA2, high temperature requirement protein A; IAPs, Inhibitor of Apoptosis Proteins; MOMP, mitochondrial outer membrane permeabilization; PARP, Poly (ADP-ribose) Polymerase; ROS, reactive oxygen species; Smac, second mitochondria-derived activator of caspase; TNF, tumor necrosis factor; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand; apoptosis; betulinic acid; cancer; mitochondria; zVAD.fmk, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone.