Avicins: triterpenoid saponins from Acacia victoriae (Bentham) induce apoptosis by mitochondrial perturbation.
Anticancer agents target various subcellular components and trigger apoptosis in chemosensitive cells. We have recently reported the tumor cell growth inhibitory properties of a mixture of triterpenoid saponins obtained from an Australian desert tree (Leguminosae) Acacia victoriae (Bentham). Here we report the purification of this mixture into two biologically pure components called avicins that contain an acacic acid core with two acyclic monoterpene units connected by a quinovose sugar. We demonstrate that the mixture of triterpenoid saponins and avicins induce apoptosis in the Jurkat human T cell line by affecting the mitochondrial function. Avicin G induced cytochrome c release within 30-120 min in whole cells and within a minute in the cell-free system. Caspase inhibitors DEVD or zVAD-fmk had no effect on cytochrome c release, suggesting the direct action of avicin G on the mitochondria. Activation of caspase-3 and total cleavage of poly(ADP-ribose) polymerase (PARP) occurred between 2 and 6 h posttreatment with avicins by zVAD-fmk. Interestingly, in the treated cells no significant changes in the membrane potential preceded or accompanied cytochrome c release. A small decrease in the generation of reactive oxygen species (ROS) was measured. The study of these evolutionarily ancient compounds may represent an interesting paradigm for the application of chemical ecology and chemical biology to human health.
Haridas
V
V
Department of Molecular Therapeutics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Higuchi
M
M
Jayatilake
G S
GS
Bailey
D
D
Mujoo
K
K
Blake
M E
ME
Arntzen
C J
CJ
Gutterman
J U
JU
D017209:Apoptosis / Q000187:drug effects*; D002240:Carbohydrate Sequence; D020169:Caspases / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D019169:Jurkat Cells; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D008969:Molecular Sequence Data; D017382:Reactive Oxygen Species; D019685:Rosales / Q000737:chemistry*; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014315:Triterpenes / Q000737:chemistry*
D003574:Cytochrome c Group; D017382:Reactive Oxygen Species; D012503:Saponins; D014315:Triterpenes; D020169:Caspases