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.
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Authors | Mingyue Song, Noppawat Charoensinphon, Xian Wu, Jinkai Zheng, Zili Gao, Fei Xu, Minqi Wang, Hang Xiao |
Journal | Journal of agricultural and food chemistry
(J Agric Food Chem)
Vol. 64
Issue 24
Pg. 4943-9
(Jun 22 2016)
ISSN: 1520-5118 [Electronic] United States |
PMID | 27219898
(Publication Type: Journal Article)
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Chemical References |
- 5-demethylnobiletin
- Flavones
- Plant Extracts
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Topics |
- Animals
- Apoptosis
(drug effects)
- Carcinoma, Non-Small-Cell Lung
(drug therapy, physiopathology)
- Cell Cycle Checkpoints
(drug effects)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Citrus
(chemistry)
- Flavones
(metabolism, pharmacology)
- Humans
- Lung Neoplasms
(drug therapy, physiopathology)
- Mice
- Plant Extracts
(metabolism, pharmacology)
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