Induction of apoptosis by Moutan Cortex Radicis in human gastric cancer cells through the activation of caspases and the AMPK signaling pathwayopen access
- Authors
- Park, Cheol; Han, Min-Ho; Park, Shin-Hyung; Hong, Su-Hyun; Kim, Gi-Young; Moon, Sung-Kwon; Kim, Wun-Jae; Choi, Yung Hyun
- Issue Date
- May-2017
- Publisher
- SOC BRASILEIRA FARMACOGNOSIA
- Keywords
- Moutan Cortex Radicis; Gastric cancer; Apoptosis; Caspase; AMPK
- Citation
- REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY, v.27, no.3, pp 315 - 323
- Pages
- 9
- Journal Title
- REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY
- Volume
- 27
- Number
- 3
- Start Page
- 315
- End Page
- 323
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/4541
- DOI
- 10.1016/j.bjp.2016.11.003
- ISSN
- 0102-695X
1981-528X
- Abstract
- Moutan Cortex Radicis, the root bark of Paeonia x suffruticosa Andrews, Paeoniaceae, has been widely used in traditional medicine therapy. Although it has been shown to possess many pharmacological activities, the molecular mechanisms of its anti-cancer activity have not been clearly elucidated. In the present study, we investigated the pro-apoptotic effects of the ethanol extract of Moutan Cortex Radicis in human gastric cancer AGS cells. Moutan Cortex Radicis treatment inhibited the cell viability of AGS cells in a concentration-dependent manner, which was associated with apoptotic cell death. Moutan Cortex Radicis's induction of apoptosis was connected with the upregulation of death receptor 4, death receptor 5, tumor necrosis factor-related apoptosis-inducing ligand, Fas ligand, and Bax, and the downregulation of Bcl-2 and Bid. Moutan Cortex Radicis treatment also induced the loss of mitochondrial membrane potential (Delta psi m), the proteolytic activation of caspases (-3, -8, and -9), and the degradation of poly(ADPribose) polymerase, an activated caspase-3 substrate protein. However, the pre-treatment of a caspase-3 inhibitor significantly attenuated Moutan Cortex Radicis-induced apoptosis and cell viability reduction. In addition, Moutan Cortex Radicis treatment effectively activated the adenosine monophosphate-activated protein kinase signaling pathway; however, a specific inhibitor of AMPK significantly reduced Moutan Cortex Radicis-induced apoptosis. Overall, the results suggest that the apoptotic activity of Moutan Cortex Radicis may be associated with a caspase-dependent cascade through the activation of both extrinsic and intrinsic signaling pathways connected with adenosine monophosphate-activated protein kinase activation, and Moutan Cortex Radicis as an activator of adenosine monophosphate-activated protein kinase could be a prospective application to treat human cancers. (C) 2016 Sociedade Brasileira de Farmacognosia. Published by Elsevier Editora Ltda.
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