Ophiopogonin D, a Steroidal Glycoside Abrogates STAT3 Signaling Cascade and Exhibits Anti-Cancer Activity by Causing GSH/GSSG Imbalance in Lung Carcinoma

被引:77
作者
Lee, Jong Hyun [1 ]
Kim, Chulwon [1 ]
Lee, Seok-Geun [1 ]
Sethi, Gautam [2 ]
Ahn, Kwang Seok [1 ]
机构
[1] Kyung Hee Univ, Coll Korean Med, Dept Sci Korean Med, 24 Kyungheedae Ro, Seoul 02447, South Korea
[2] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore 117600, Singapore
来源
CANCERS | 2018年 / 10卷 / 11期
基金
新加坡国家研究基金会;
关键词
ophiopogonin D; STAT3; ROS; GSH; apoptosis; NSCLC; INHIBITS TUMOR-GROWTH; HEPATOCELLULAR-CARCINOMA; AQUEOUS EXTRACT; IN-VITRO; CANCER; PROLIFERATION; APOPTOSIS; TRANSDUCER; MODULATION; ACTIVATION;
D O I
10.3390/cancers10110427
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Natural medicinal plants are multi-targeted in nature and their anti-cancer activities are also complex and varied, thus requiring a more systematic analysis of their modes of action. Since the activation of signal transducer and activator of transcription 3 (STAT3) is often deregulated in non-small cell lung carcinoma (NSCLC) cells and tissue specimens, its negative regulation can form the basis for identification of targeted therapy. In this report, we analyzed the possible anti-cancer effects of ophiopogonin D (OP-D) and the underlying mechanisms by which OP-D exerts its actions in NSCLC. OP-D exhibited substantial suppressive activity on STAT3 signaling and this effect was found to be mediated via oxidative stress phenomena caused by disturbance in GSH/GSSG ratio. In addition, OP-D induced apoptosis, activated caspase mediated apoptotic cascade and decreased expression of various oncogenic genes. Consistently, OP-D treatment significantly reduced NSCLC tumor growth in preclinical mouse model with via decreasing levels of p-STAT3. OP-D was also found to attenuate the expression of STAT3-regulated anti-apoptosis, cell cycle regulator, and angiogenesis biomarkers. Our findings suggest that OP-D can induce apoptosis and exert anti-tumor effects by inhibition of STAT3 signaling pathways in NSCLC.
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页数:16
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