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Inhibition of Lung Cancer Cell Growth by Polymethoxyflavones from Sweet Orange
Author(s) -
Charoensinphon Noppawat,
Qiu Peiju,
Dong Ping,
Ngauv Pearline,
Xiao Hang
Publication year - 2010
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.24.1_supplement.217.8
Subject(s) - nobiletin , apoptosis , cell cycle , cell growth , chemistry , cancer cell , cell , annexin , cell cycle checkpoint , lung cancer , acridine orange , growth inhibition , microbiology and biotechnology , cancer research , biology , biochemistry , medicine , cancer , flavonoid , antioxidant
We isolated 6 closely related polymethoxyflavones (PMFs) from sweet orange, and studied their effects on the growth of two human non‐small cell lung cancer cells. The permethoxylated PMFs, namely nobiletin, 3,5,6,7,8,3′,4′‐heptamethoxyflavone (HMF), and tangeretin, showed dose dependant growth inhibition on H1299 and H460 cells. Interestingly, three monohydroxylated PMFs, namely 5‐hydroxyl nobiletin (5HN), 5‐hydroxyl HMF (5HH), and 5‐hydroxyl tangeretin (5HT), that are derived from the three permethoxylated PMFs correspondingly showed much stronger inhibitory effects on the same lung cancer cells than their counterparts. In H460 cells, IC 50 of 5HN, 5HH, and 5HT were 6.3, 17.8, and 44.0‐fold lower than those of their permethoxylated counterparts, respectively. Cell cycle analysis revealed that all 6 PMFs caused cell cycle arrest at G0/G1 phase, while 5HH and 5HT also increased G2/M cell population. The Annexin V/PI co‐staining assay revealed that PMFs had different effects on cell death. While other PMFs showed marginal effects on the apoptosis, 5HH and 5HT significantly increased percentage of lung cancer cells undergoing early and late apoptosis by 4 to 6 fold in comparison with the control cells. Our results demonstrated that hydroxylation in the PMF structures enhanced their growth inhibitory effects on human lung cancer cells by potentiating their activities on cell cycle arrest and pro‐apoptosis. Grant Funding Source: University of Massachusetts Amherst