Targeting mitochondrial apoptosis by betulinic acid in human cancers.

Betulinic acid (BA) is a naturally occurring pentacyclic triterpene that exhibits a variety of biological activities including potent antitumor properties. This anticancer activity has been linked to its ability to directly trigger mitochondrial membrane permeabilization, a central event in the apoptotic process that seals the cell's fate. In contrast to the potent cytotoxicity of BA against a variety of cancer types, non-neoplastic cells as well as normal tissue remain relatively resistant to BA, thus pointing to a therapeutic window. Because agents that exert a direct action on mitochondria may bypass resistance to conventional chemotherapeutics, there is increasing interest to develop such compounds as experimental cancer therapeutics. Thus, mitochondrion-targeted agents such as BA hold great promise as a novel approach to overcome certain forms of drug resistance in human cancers.