Licochalcone A Suppresses the Proliferation of Osteosarcoma Cells through Autophagy and ATM-Chk2 Activation

被引:32
作者
Shen, Tai-Shan [1 ]
Hsu, Yung-Ken [1 ]
Huang, Yi-Fu [2 ]
Chen, Hsuan-Ying [2 ]
Hsieh, Cheng-Pu [1 ,2 ]
Chen, Chiu-Liang [1 ,3 ]
机构
[1] Changhua Christian Hosp, Dept Orthoped Surg, Changhua 50006, Taiwan
[2] Changhua Christian Hosp, Orthoped & Sports Med Lab, Changhua 50006, Taiwan
[3] Da Yeh Univ, Dept Nursing, Changhua 51591, Taiwan
来源
MOLECULES | 2019年 / 24卷 / 13期
关键词
Licochalcone A; ATM-Chk2; autophagy; osteosarcoma; ATM ACTIVATION; APOPTOSIS; CANCER; INACTIVATION; DEATH;
D O I
10.3390/molecules24132435
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Licochalcone A, a flavonoid extracted from licorice root, has been shown to exhibit broad anti-inflammatory, anti-bacterial, anticancer, and antioxidative bioactivity. In this study, we investigated the antitumor activity of Licochalcone A against human osteosarcoma cell lines. The data showed that Licochalcone A significantly suppressed cell viability in MTT assay and colony formation assay in osteosarcoma cell lines. Exposure to Licochalcone A blocked cell cycle progression at the G2/M transition and induced extrinsic apoptotic pathway in osteosarcoma cell lines. Furthermore, we found the Licochalcone A exposure resulted in rapid ATM and Chk2 activation, and high levels of nuclear foci of phosphorylated Chk2 at Thr 68 site in osteosarcoma cell lines. In addition, Licochalcone A exposure significantly induced autophagy in osteosarcoma cell lines. When Licochalcone A-induced autophagy was blocked by the autophagy inhibitor chloroquine, the expression of activated caspase-3 and Annexin V positive cells were reduced, and cell viability was rescued in Licochalcone A-treated osteosarcoma cell lines. These data indicate that the activation of ATM-Chk2 checkpoint pathway and autophagy may contribute to Licochalcone A-induced anti-proliferating effect in osteosarcoma cell lines. Our findings display the possibility that Licochalcone A may serve as a potential therapeutic agent against osteosarcoma.
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页数:12
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