Identification of 3-O-α-l-arabinosyl oleanolic acid, a triterpenoid saponin, as a new breast cancer stem cell growth inhibitor

This study was conducted to determine the anti-cancer activity of 3-O-α-L-arabinosyl oleanolic acid (3-O-L-AO), a triterpenoid saponin, isolated from the leaves of Schumacheria castaneifolia Vahl in breast cancer stem cells (bCSCs) grown in hypoxia. Anti-proliferative effects of 3-O-L-AO in bCSCs were determined using WST-1 assay. Real-time PCR was employed to evaluate the effects of 3-O-L-AO on apoptosis. Compound 3-O-L-AO exerted greater anti-proliferative effect in bCSCs grown under hypoxic conditions. Treatment of bCSCs with 3-O-L-AO resulted in a significant up-regulation of Bax and p53 and a significant down-regulation of survivin, HIF-1α and HIF-2α. Activation of caspase 3/7 activity and apoptosis-related morphological changes in bCSCs exposed to 3-O-L-AO further confirmed that 3-O-L-AO can induce apoptosis. Collectively, the results obtained indicated that 3-O-L-AO can be considered as a new anti-cancer agent to target chemo- and radio-therapy-resistant bCSCs.