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Mol Nutr Food Res. 2013 Dec;57(12):2103-11. doi: 10.1002/mnfr.201300136. Epub 2013 Aug 8.

5-demethyltangeretin inhibits human nonsmall cell lung cancer cell growth by inducing G2/M cell cycle arrest and apoptosis.

Author information

1
Department of Food Science, University of Massachusetts, Amherst, MA, USA.

Abstract

SCOPE:

Tangeretin (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 RESULTS:

Cell viability assay demonstrated that 5DT inhibited NSCLC cell growth in a time- and dose-dependent manner, and IC50 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.

CONCLUSION:

Our 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.

KEYWORDS:

5-Demethyltangeretin; 5-Hydroxy-6,7,8,4′-tetramethoxyflavone; Apoptosis; Lung cancer; Tangeretin

PMID:
23926120
PMCID:
PMC4648632
DOI:
10.1002/mnfr.201300136
[Indexed for MEDLINE]
Free PMC Article

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