Author:
Haridas Valsala,Higuchi Masahiro,Jayatilake Gamini S.,Bailey David,Mujoo Kalpana,Blake Mary E.,Arntzen Charles J.,Gutterman Jordan U.
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.
Publisher
Proceedings of the National Academy of Sciences
Cited by
178 articles.
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