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KMID : 1134820170460040417
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Journal of the Korean Society of Food Science and Nutrition
2017 Volume.46 No. 4 p.417 ~ p.425
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Ethanol Extract from Cnidium monnieri (L.) Cusson Induces G1 Cell Cycle Arrest by Regulating Akt/GSK-3β/p53 Signaling Pathways in AGS Gastric Cancer Cells
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Lim Eun-Gyeong
Kim Eun-Ji
Kim Bo-Min
Kim Sang-Yong
Ha Sung-Ho
Kim Young-Min
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Abstract
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Cnidium monnieri (L.) Cusson is distributed in China and Korea, and the fruit of C. monnieri is used as traditional Chinese medicine to treat carbuncle and pain in female genitalia. In this study, we examined the anti-proliferation and cell cycle arrest effects of ethanol extracts from C. monnieri (CME) in AGS gastric cancer cells. Our results show that CME suppressed cell proliferation and induced release of lactate dehydrogenase (LDH) in AGS cells by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and LDH assay. Cell morphology was altered by CME in a dose-dependent manner. In order to identify the cell cycle arrest effects of CME, we investigated cell cycle analysis after CME treatment. In our results, CME induced cell cycle arrest at G1 phase. Protein kinase B (Akt) plays a major role in cell survival mechanisms such as growth, division, and metastasis. Akt protein regulates various downstream proteins such as glycogen synthase kinase-3β (GSK-3β) and tumor protein p53 (p53). Expression levels of p-Akt, p-GSK-3β, p53, p21, cyclin E, and cyclin-dependent kinase 2 (CDK2) were determined by Western blot analysis. Protein levels of p-Akt, p-GSK-3β, and cyclin E were reduced while those of p53, p21, and p-CDK2 (T14/Y15) were elevated by CME. Moreover, treatment with CME, LY294002 (phosphoinositide 3-kinase/Akt inhibitor), BIO (GSK-3β inhibitor), and Pifithrin-α (p53 inhibitor) showed that cell cycle arrest effects were mediated through regulation of the Akt/GSK-3β/p53 signaling pathway. These results suggest that CME induces cell cycle arrest at G1 phase via the Akt/GSK-3β/p53 signaling pathway in AGS gastric cancer cells.
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KEYWORD
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Akt/GSK-3β/p53 signaling pathway, AGS, ethanol extracts from Cnidium monnieri, G1 arrest
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