Article Publish Status: FREE
Abstract Title:

Induction of Apoptosis by Citrus unshiu Peel in Human Breast Cancer MCF-7 Cells: Involvement of ROS-Dependent Activation of AMPK.

Abstract Source:

Biol Pharm Bull. 2018 ;41(5):713-721. PMID: 29709909

Abstract Author(s):

Min Yeong Kim, Hyun Hwang Bo, Eun Ok Choi, Da He Kwon, Hong Jae Kim, Kyu Im Ahn, Seon Yeong Ji, Jin-Woo Jeong, Shin-Hyung Park, Su-Hyun Hong, Gi-Young Kim, Cheol Park, Heui-Soo Kim, Sung-Kwon Moon, Seok-Joong Yun, Wun Jae Kim, Yung Hyun Choi

Article Affiliation:

Min Yeong Kim


The fruit of Citrus unshiu MARKOVICH used for various purposes in traditional medicine has various pharmacological properties including antioxidant, anti-inflammatory, and antibacterial effects. Recently, the possibility of anti-cancer activity of the extracts or components of this fruit has been reported; however, the exact mechanism has not yet been fully understood. In this study, we evaluated the anti-proliferative effect of water extract of C. unshiu peel (WECU) on human breast cancer MCF-7 cells and investigated the underlying mechanism. Our results showed that reduction of MCF-7 cell survival by WECU was associated with the induction of apoptosis. WECU-induced apoptotic cell death was related to the activation of caspase-8 and -9, representative initiate caspases of extrinsic and intrinsic apoptosis pathways, respectively, and increase in the Bax : Bcl-2 ratio accompanied by cleavage of poly(ADP-ribose) polymerase (PARP). WECU also increased the mitochondrial dysfunction and cytosolic release of cytochrome c. In addition, AMP-activated protein kinase (AMPK) and its downstream target molecule, acetyl-CoA carboxylase, were activated in aconcentration-dependent manner in WECU-treated cells. In contrast, compound C, an AMPK inhibitor, significantly inhibited WECU-induced apoptosis, while inhibiting increased expression of Bax and decreased expression of Bcl-2 by WECU and inhibition of WECU-induced PARP degradation. Furthermore, WECUprovoked the production of reactive oxygen species (ROS); however, the activation of AMKP and apoptosis by WECU were prevented, when the ROS production was blocked by antioxidant N-acetyl cysteine. Therefore, our data indicate that WECU suppresses MCF-7 cell proliferation by activating the intrinsicand extrinsic apoptosis pathways through ROS-dependent AMPK pathway activation.

Study Type : In Vitro Study

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