Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 57, Issue 12, Pages 2103-2111Publisher
WILEY
DOI: 10.1002/mnfr.201300136
Keywords
Apoptosis; 5-Demethyltangeretin; 5-Hydroxy-6; 7; 8; 4-tetramethoxyflavone; Lung cancer; Tangeretin
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Funding
- NIH [CA139174]
- AICR
- USDA
- Div Of Biological Infrastructure
- Direct For Biological Sciences [1126366] Funding Source: National Science Foundation
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ScopeTangeretin (TAN) and 5-demethyltangeretin (5DT) are two closely related polymethoxyflavones found in citrus fruits. We investigated growth inhibitory effects on three human nonsmall cell lung cancer (NSCLC) cells. Methods and resultsCell viability assay demonstrated that 5DT inhibited NSCLC cell growth in a time- and dose-dependent manner, and IC(50)s of 5DT were 79-fold, 57-fold, and 56-fold lower than those of TAN in A549, H460, and H1299 cells, respectively. Flow cytometry analysis showed that 5DT induced extensive G2/M cell cycle arrest and apoptosis in NSCLC cells, while TAN at tenfold higher concentrations did not. The apoptosis induced by 5DT was further confirmed by activation of caspase-3 and cleavage of PARP. Moreover, 5DT dose-dependently upregulated p53 and p21(Cip1/Waf1), and downregulated Cdc-2 (Cdk-1) and cyclin B1. HPLC analysis revealed that the intracellular levels of 5DT in NSCLC cells were 2.7-4.9 fold higher than those of TAN after the cells were treated with 5DT or TAN at the same concentration. ConclusionOur results demonstrated that 5DT inhibited NSCLC cell growth by inducing G2/M cell cycle arrest and apoptosis. These effects were much stronger than those produced by TAN, which is partially due to the higher intracellular uptake of 5DT than TAN.
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