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Mechanism of Juglone-Induced Cell Cycle Arrest and Apoptosis in Ishikawa Human Endometrial Cancer Cells

Zhang, Yuan-Yuan, Zhang, Fan, Zhang, Ying-Shuo, Thakur, Kiran, Zhang, Jian-Guo, Liu, Yun, Kan, Huan, Wei, Zhao-Jun
Journal of agricultural and food chemistry 2019 v.67 no.26 pp. 7378-7389
Carya cathayensis, antineoplastic agents, apoptosis, cell cycle checkpoints, cell proliferation, cyclin-dependent kinase, cyclins, high performance liquid chromatography, hulls, inhibitory concentration 50, interphase, juglone, mass spectrometry, messenger RNA, mitochondria, neoplasm cells, nuclear magnetic resonance spectroscopy, protein synthesis, uterine neoplasms
The molecular mechanism of Juglone-induced cell cycle arrest and apoptosis in human endometrial cancer cells was investigated. Juglone was purified from the green husk of Carya cathayensis Sarg and identified by HPLC, LC-MS/MS, and NMR. At an IC₅₀ of 20.81 μM, juglone significantly inhibited Ishikawa cell proliferation, as shown by S phase arrest mediated by inactivation of cyclin A protein (p < 0.05). The ROS levels increased significantly after exposure to juglone, which paralleled increases in the mRNA and protein expression of p21 and decreases in the levels of CDK2, cdc25A, CHK1, and cyclin A. The expression of Bcl-2 and Bcl-xL was significantly down-regulated, whereas the expression of Bax, Bad and cyto c was up-regulated, and we later confirmed the involvement of the mitochondrial pathway in juglone-induced apoptosis. Our in vitro results stated that juglone can be studied further as an effective natural anticancer agent.