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.
Fulda
Simone
S
University Children's Hospital, Eythstr. 24, D-89075 Ulm, Germany. simone.fulda@uniklinik-ulm.de
Kroemer
Guido
G
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D051336:Mitochondrial Membranes / Q000187:drug effects*; D008954:Models, Biological; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D053978:Pentacyclic Triterpenes; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000094062:Betulinic Acid
D000972:Antineoplastic Agents, Phytogenic; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D000094062:Betulinic Acid