Avicins: Triterpenoid saponins from Acacia victoriae (Bentham) induce apoptosis by mitochondrial perturbation
- 8 May 2001
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 98 (10) , 5821-5826
- https://doi.org/10.1073/pnas.101619098
Abstract
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.Keywords
This publication has 45 references indexed in Scilit:
- Mitochondrion as a Novel Target of Anticancer ChemotherapyJNCI Journal of the National Cancer Institute, 2000
- Mitochondrial EvolutionScience, 1999
- Apoptosis Induction by Caspase-8 Is Amplified through the Mitochondrial Release of Cytochrome cJournal of Biological Chemistry, 1998
- Caspases: killer proteasesTrends in Biochemical Sciences, 1997
- The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of ApoptosisScience, 1997
- Programmed Cell Death in Animal DevelopmentCell, 1997
- Plant-derived anticancer agentsBiochemical Pharmacology, 1997
- Mitochondria and programmed cell death: back to the futureFEBS Letters, 1996
- Apoptosis in the Pathogenesis and Treatment of DiseaseScience, 1995
- Oncogenes and cell deathCurrent Opinion in Genetics & Development, 1994