Inhibitory Effects of Quercetin on Progression of Human Choriocarcinoma Cells Are Mediated Through PI3K/AKT and MAPK Signal Transduction Cascades

绒毛膜癌 PI3K/AKT/mTOR通路 蛋白激酶B MAPK/ERK通路 槲皮素 信号转导 细胞凋亡 细胞生长 细胞生物学 生物 癌细胞 癌症研究 紫杉醇 磷酸化 药理学 化学 生物化学 癌症 抗氧化剂 遗传学
作者
Whasun Lim,Changwon Yang,Sunwoo Park,Fuller W. Bazer,Gwonhwa Song
出处
期刊:Journal of Cellular Physiology [Wiley]
卷期号:232 (6): 1428-1440 被引量:30
标识
DOI:10.1002/jcp.25637
摘要

As a major dietary flavonol, quercetin mitigates proliferation and progression of cancer due to its anti-angiogenic, anti-inflammatory, anti-oxidant, and apoptotic biological effects on cells. Although its apoptotic effects have been reported for various cancers, little is known of the functional role of quercetin in gestational choriocarcinoma. Results of the present study indicated that quercetin reduced proliferation and induced cell death in two choriocarcinoma cell lines, JAR and JEG3 cells, with an increase in the sub-G1 phase of the cell cycle. In addition, quercetin induced mitochondrial dysfunction significantly reduced mitochondrial membrane potential (MMP) and increased production of reactive oxygen species (ROS) in both JAR and JEG3 cells. Further, quercetin inhibited phosphorylation of AKT, P70S6K and S6 proteins whereas, it increased phosphorylation of ERK1/2, P38, JNK and P90RSK proteins in JAR and JEG3 cells. The decrease in viability of choriocarcinoma cells treated with quercetin was confirmed by using combinations of quercetin and pharmacological inhibitors of the PI3K and MAPK signaling pathways. Classical chemotherapeutic agents, cisplatin (a platinum-based drug) and paclitaxel (a taxene-based drug), inhibited proliferation of JAR and JEG3 cells, and when combined with quercetin, the antiproliferative effects of cisplatin and paclitaxel were enhanced for both choriocarcinoma cell lines. Collectively, these results suggest that quercetin prevents development of choriocarcinoma and may be a valuable therapeutic agent for treatment of choriocarcinoma through its regulation of PI3K and MAPK signal transduction pathways. J. Cell. Physiol. 232: 1428-1440, 2017. © 2016 Wiley Periodicals, Inc.
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