Premium
Inhibitory Effects of 5‐hydroxy Tangeretin on Human Non‐Small Cell Lung Cancer Cells
Author(s) -
Charoensinphon Noppawat,
Qiu Peiju,
Dong Ping,
Zheng Jinkai,
Ngauv Pearline,
Xiao Hang
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.979.15
Subject(s) - apoptosis , cell cycle , cell growth , cell cycle checkpoint , chemistry , a549 cell , cancer cell , annexin , cancer research , cancer , biology , biochemistry , medicine
Tangeretin and 5‐hydroxy‐tangeretin (5HT) are polymethoxyflavones found in citrus peels. We investigated their inhibitory effects on 3 human non‐small cell lung cancer cell lines. The results showed that 5HT significantly inhibited cancer cell growth in a time‐ and dose‐dependent manner, and these effects were much stronger than those produced by tangeretin. For example, IC 50 s of 5HT were 78.9‐fold, 57.2‐fold and 56.3‐fold lower than those of tangeretin in A549, H460, and H1299 cells, respectively. Cell cycle analysis showed that 5HT induced G2/M arrest in all 3 cancer cell lines, while tangeretin did not change cell cycle distribution. Annexin V/PI co‐staining assay showed that 5HT induced extensive apoptosis in all 3 cancer cells, while tangeretin at 10‐fold higher concentrations did not. The apoptosis induced by 5HT was further confirmed by activation of caspase‐3 and cleavage of PARP in all 3 lung cancer cell lines after 5HT treatments. Moreover, 5HT dose‐dependently upregulated p53 and p21 (Cip1/Waf1) , and downregulated cdc‐2 (cdk‐1) and cyclinB1 in A549 and H460 cells. Overall, our results demonstrated that 5HT inhibited lung cancer cell growth by inducing cell cycle arrest and apoptosis, and hydroxylation at 5 position in 5HT played pivotal roles in its enhanced anticancer activities compared with tangeretin. Grant Funding Source : NIH (CA139174), CEAR pilot grant, and USDA Special Grant on Bioactive Foods