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论文类型：期刊论文

发表时间：2015-12-01

发表刊物：APOPTOSIS

收录刊物：SCIE、PubMed、Scopus

卷号：20

期号：12

页面范围：1636-1650

ISSN号：1360-8185

关键字：SZC017; Oleanolic acid derivative; Apoptosis; Autophagy; Breast cancer cells

摘要：Oleanolic acid (OA) and its derivatives such as 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), CDDO-Me, and CDDO-Im show potent anticancer function. In this study, we elucidated the anticancer effect of SZC017, a novel OA derivative and identified the mechanisms by which SZC017 induces MCF-7 cell death. We found that SZC017 effectively decreased the cell viability of these breast cancer cells, but was less toxic to MCF10A mammary epithelial cells. Mechanisms underlying the inhibition of cell viability are apoptosis, autophagy induction, and G(0)/G(1) phase arrest. SZC017 treatment suppressed the levels of Akt, phosphorylated-Akt (p-Akt), p-I kappa B alpha, total p65, and total p-p65, in addition to p-p65 in both the cytoplasm and nucleus. Furthermore, the inhibition of p65 nuclear translocation was confirmed by immunofluorescence staining. Cell viability was increased after pretreatment with chloroquine, an inhibitor of autophagy, whereas the level of procaspase-3 was significantly decreased. A concentration-dependent increase in the intracellular reactive oxygen species (ROS) level was observed in both MCF-7 and MDA-MB-231 cells. Additionally, pretreatment with N-acetyl-l-cysteine (NAC), a ROS scavenger, increased cell viability and the expression of Akt and procaspase-3, but decreased the ratio of LC3-II/I. These data show that SZC017 is an effectively selective anticancer agent against breast cancer cells, highlighting the potential use of this derivative as a breast cancer therapeutic agent.