title: SZC017, a novel oleanolic acid derivative, induces apoptosis and autophagy in human breast cancer cells.
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.
authors.affiliation: Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lyshun, Dalian, Liaoning, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lyshun, Dalian, Liaoning, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lyshun, Dalian, Liaoning, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lyshun, Dalian, Liaoning, China.
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lyshun, Dalian, Liaoning, China.
authors.forename: Jingjun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lyshun, Dalian, Liaoning, China.
authors.forename: Shumin
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lyshun, Dalian, Liaoning, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Chu
authors.affiliation: Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lyshun, Dalian, Liaoning, China.
authors.forename: Zhengwu
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lyshun, Dalian, Liaoning, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lyshun, Dalian, Liaoning, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lyshun, Dalian, Liaoning, China.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lyshun, Dalian, Liaoning, China.
authors.forename: Guozhu
authors.initials: G
authors.lastname: Han
authors.affiliation: College of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, Liaoning, China.
authors.forename: Shisheng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lyshun, Dalian, Liaoning, China. tangzeyao@aliyun.com.
authors.forename: Zeyao
authors.initials: Z
authors.lastname: Tang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D009828:Oleanolic Acid / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D009828:Oleanolic Acid; D053148:Caspase 3
keywords: Apoptosis; Autophagy; Breast cancer cells; Oleanolic acid derivative; SZC017