[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.5352/JLS.2019.29.4.410

Relationship between Reactive Oxygen Species and Adenosine Monophosphate-activated Protein Kinase Signaling in Apoptosis Induction of Human Breast Adenocarcinoma MDA-MB-231 Cells by Ethanol Extract of Citrus unshiu Peel

Kim, Min Yeong (Department of Biochemistry, Dong-eui University College of Korean Medicine)
HwangBo, Hyun (Department of Biochemistry, Dong-eui University College of Korean Medicine)
Ji, Seon Yeong (Department of Biochemistry, Dong-eui University College of Korean Medicine)
Hong, Su-Hyun (Department of Biochemistry, Dong-eui University College of Korean Medicine)
Choi, Sung Hyun (Department of System Management, Korea Lift College)
Kim, Sung Ok (Department of Food Science and Biotechnology, College of Engineering, Kyungsung University)
Park, Cheol (Department of Molecular Biology, College of Natural Sciences, Dong-eui University)
Choi, Yung Hyun (Department of Biochemistry, Dong-eui University College of Korean Medicine)

Publication Information

Journal of Life Science / v.29, no.4, 2019 , pp. 410-420 More about this Journal

Abstract

Citrus unshiu peel extracts possess a variety of beneficial effects, and studies on their anticancer activity have been reported. However, the exact mechanisms underlying this activity remain unclear. In the current study, the apoptotic effect of ethanol extract of C. unshiu peel (EECU) on human breast adenocarcinoma MDA-MB-231 cells and related mechanisms were investigated. The results showed that the survival rate of MDA-MB-231 cells treated with EECU was significantly inhibited in a concentration-dependent manner, which was associated with the induction of apoptosis. EECU-induced apoptosis was associated with the activation of caspase-8 and caspase-9, which initiate extrinsic and intrinsic apoptosis pathways, respectively, and caspase-3, a representative effect caspase. EECU suppressed the expression of the inhibitor of apoptosis family of proteins, leading to an increased Bax/Bcl-2 ratio and proteolytic degradation of poly (ADP-ribose) polymerase. EECU also enhanced the loss of the mitochondrial membrane potential and cytochrome c release from the mitochondria to the cytosol, along with truncation of Bid. In addition, EECU activated AMP-activated protein kinase (AMPK), and compound C, an AMPK inhibitor, significantly weakened EECU-induced apoptosis and cell viability reduction. Furthermore, EECU promoted the generation of reactive oxygen species (ROS), which acted as upstream signals for AMPK activation as pretreatment of cells, with the antioxidant N-acetyl cysteine reversing both EECU-induced AMPK activation and apoptosis. Collectively, these findings suggest that EECU inhibits MDA-MB-231 adenocarcinoma cell proliferation by activating intrinsic and extrinsic apoptotic pathways, which was mediated through ROS/AMPK-dependent pathways.

Keywords

AMPK; apoptosis; breast cancer cells; Citrus unshiu peel; ROS;

Citations & Related Records

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