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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

Mingyue Song, Noppawat Charoensinphon, Xian Wu, Jinkai Zheng, Zili Gao, Fei Xu, Minqi Wang, Hang Xiao

J Agric Food Chem. 2016 Jun 22;64(24):4943-9.

PMID: 27219898

Abstract:

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 5DN and its metabolites for chemoprevention of lung cancer.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP2174596	5-Demethylnobiletin		2174-59-6	Price

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