Several studies have shown how
pentacyclic triterpenes can inhibit proliferation and induce apoptosis of some tumor cell lines; however, its effect on astrocytic
tumors, one of the most malignant forms of
cancer, has rarely been reported. The aim of this study was to examine how the
pentacyclic triterpenes,
oleanolic acid and
maslinic acid, isolated from olive juice, affected
astrocytoma cell morphology and survival. Cell proliferation was inhibited in 1321N1
astrocytoma cells by using 1 to 50 micromol/L of either
oleanolic acid or
maslinic acid, with an average IC(50) of 25 micromol/L. Growth inhibition led to morphologic and cytoskeletal alterations associated with the loss of stellate morphology and characterized by a retraction of the cytoplasm and collapse of actin stress fibers. Using
4',6-diamidino-2-phenylindole and
Annexin V, we showed that
astrocytoma cell death induced by
oleanolic acid or
maslinic acid were mainly due to apoptotic events. Furthermore, we showed that
caspase-3 is activated as a consequence of
triterpene treatment. Finally, we found that exposure of the cells to
oleanolic acid or
maslinic acid resulted in a significant increase of intracellular
reactive oxygen species, followed by loss of mitochondrial membrane integrity. Importantly, enzymatic scavengers, such as
catalase, or phenolic
antioxidants, such as
butylated hydroxytoluene, rescued cells from the
triterpene-mediated apoptosis, suggesting that the potential
therapeutic effect of these acidic
triterpenes is dependent on oxidative stress. Our data show that acidic
triterpenes play a major role in 1321N1
astrocytoma morphology and viability and support the conclusion that
oleanolic acid and
maslinic acid may thus be promising new agents in the management of
astrocytomas.