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SZC017, a novel oleanolic acid derivative, induces apoptosis and autophagy in human breast cancer cells

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Abstract

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 G0/G1 phase arrest. SZC017 treatment suppressed the levels of Akt, phosphorylated-Akt (p-Akt), p-IκBα, 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.

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Acknowledgments

This work was supported by the Natural Science Foundation of China (No. 30772601) and the University Innovation Team Project Foundation of Education Department of Liaoning Province (No. LT2013019).

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Authors and Affiliations

  1. Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lyshun, Dalian, Liaoning, China

    Lei Gao, Yan Wang, Zhen Xu, Xiaorui Li, Jingjun Wu, Shumin Liu, Peng Chu, Zhengwu Sun, Bin Sun, Yuan Lin, Jinyong Peng, Guozhu Han & Zeyao Tang

  2. College of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, Liaoning, China

    Shisheng Wang

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  1. Lei Gao
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Gao, L., Wang, Y., Xu, Z. et al. SZC017, a novel oleanolic acid derivative, induces apoptosis and autophagy in human breast cancer cells. Apoptosis 20, 1636–1650 (2015). https://doi.org/10.1007/s10495-015-1179-0

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