title: Inhibitory Effects of Metabolites of 5-Demethylnobiletin on Human Nonsmall Cell Lung Cancer Cells.
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.
authors.affiliation: Department of Food Science, University of Massachusetts , Amherst, Massachusetts 01003, United States.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Song
authors.affiliation: Department of Food Science, University of Massachusetts , Amherst, Massachusetts 01003, United States.
authors.forename: Noppawat
authors.initials: N
authors.lastname: Charoensinphon
authors.affiliation: Department of Food Science, University of Massachusetts , Amherst, Massachusetts 01003, United States.
authors.forename: Xian
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Food Science, University of Massachusetts , Amherst, Massachusetts 01003, United States.|Institute of Agro-Products Processing Science and Technology, Chinese Academy of Agricultural Sciences , Beijing 100081, P.R. China.
authors.forename: Jinkai
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Food Science, University of Massachusetts , Amherst, Massachusetts 01003, United States.
authors.forename: Zili
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Food Science, University of Massachusetts , Amherst, Massachusetts 01003, United States.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Food Science, University of Massachusetts , Amherst, Massachusetts 01003, United States.
authors.forename: Minqi
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Food Science, University of Massachusetts , Amherst, Massachusetts 01003, United States.|College of Bioscience and Biotechnology, Hunan Agricultural University , Changsha, 410128 Hunan P. R. China.
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000503:physiopathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002957:Citrus / Q000737:chemistry*; D047309:Flavones / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000503:physiopathology*; D051379:Mice; D010936:Plant Extracts / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C000604601:5-demethylnobiletin; D047309:Flavones; D010936:Plant Extracts
keywords: 5-demethylnobiletin; chemoprevention; lung cancer cells; metabolites; nobiletin