Oleanolic acid derivative SZC014 inhibit cell proliferation and induce apoptosis of human breast cancer cells in a ROS-dependent way

Abstract

Oleanolic acid (OA) and its derivatives are a novel emerging class of compounds. Although OA exhibits potent anticancer and anti-inflammatory function, the potential effect of its new derivatives (SZC014) in human breast cancers has not been understood yet. In this investigation, we demonstrated the anticancer effect of SZC014, a novel OA derivative and identified the possible mechanisms by which SZC014 induced MCF-7 cell death. The biological functions of SZC014 were validated by MTT, migration and colony formation assays in breast cancer cells. Cell apoptosis was monitored by Annexin V- FITC assay. Intracellular ROS and cell cycle were measured by flow cytometric analysis. Western blot was used to detect protein expression level. Our present results fully demonstrated that SZC014 inhibits breast cancer cells proliferation, colony formation, and cell migration. Further investigation verified that ROS generation, apoptosis induction and G0/G1 phase arrest was observed in SZC014-treated MCF-7 cells. However, pretreatment with N-acetyl- L-cysteine (NAC), a ROS scavenger, increased the expression of procaspase-3. Additionally, SZC014 treatment suppressed the levels of Akt, phosphorylated-Akt (p-Akt), COX-2, p-p65 in the cytoplasmic and p65 in nuclear. Furthermore, the inhibition of p65 nuclear translocation was confirmed by immunofluorescence staining. These data show that SZC014 is an effectively selective anticancer agent against breast cancer cells, highlighting the potential use of this derivative as a breast cancer therapeutic agent.