Inhibitory Effects of Metabolites of 5-Demethylnobiletin on Human Nonsmall Cell Lung Cancer Cells
Inhibitory Effects of Metabolites of 5-Demethylnobiletin on Human Nonsmall Cell Lung Cancer Cells
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DOI：
10.1021/acs.jafc.6b01367
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发表时间：
2016-06-22
影响因子：
6.1
通讯作者：
Xiao, Hang
中科院分区：
文献类型：
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作者：
Song, Mingyue;Charoensinphon, Noppawat;Xiao, Hang
5-去甲基肉桂酸是一种在柑橘类水果中发现的独特的黄酮类化合物，对人类癌症具有潜在的化学预防作用。我们先前在喂食5DN的小鼠中鉴定了5DN的三种代谢产物，即5，4 '-去二甲基诺贝尔碱（M1）、5，3'，4 '-三去甲基诺贝尔碱（M2）和5，3'-去二甲基诺贝尔碱（M3）。在此，我们研究了这三种代谢产物对NSCLC细胞的抑制作用。结果表明，M1、M2，尤其是M3对H460和H1299细胞的生长和集落形成的抑制作用强于5DN。三种代谢产物均能显著抑制A549细胞的肿瘤球形成。流式细胞仪分析表明，所有代谢产物均诱导细胞周期阻滞和细胞凋亡，这些作用也比5DN强。这些代谢产物的抑制作用与其调节与细胞增殖和凋亡相关的关键信号蛋白的能力有关。总之，我们的研究结果为利用5SDN及其代谢产物进行肺癌的化学预防提供了基础。
5-Demethylnobiletin is a unique flavonoid found in citrus fruits with potential chemopreventive effects against human cancers. We previously identified three metabolites of 5DN, namely 5,4'-didemethylnobiletin (M1), 5,3',4'-tridemethylnobiletin (M2), and 5,3'-didemethylnobiletin (M3) in mice fed 5DN. Herein, we investigated the inhibitory effects of these three metabolites on NSCLC cells. Our results demonstrated that M1, M2, and especially M3 showed stronger inhibition on the growth and colony formation of H460 and H1299 cells compared to 5DN. Three metabolites significantly inhibited the tumorsphere formation of A549 cells. Flow cytometry analysis showed that all metabolites induced cell cycle arrest and cellular apoptosis, and these effects were also stronger than that of 5DN. The inhibitory effects of these metabolites were associated with their ability to modulate the key signaling proteins related to cell proliferation and apoptosis. Overall, our results provided a basis for utilizing 5SDN and its metabolites for chemoprevention of lung cancer.