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Potent and specific effects of orally bioavailable methylated flavones on oral cancer cell proliferation
Author(s) -
Walle Thomas,
Ta Nga,
Wen Xia,
Tsuji Petra A.,
Walle U. Kristina
Publication year - 2007
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.21.6.a1099-b
Subject(s) - flavones , chrysin , cell growth , chemistry , bioavailability , cancer cell , apigenin , cell culture , pharmacology , cancer , cell , cell cycle , biochemistry , flavonoid , biology , antioxidant , chromatography , genetics
Poor oral bioavailability is a major limitation for the successful use of flavonoids as cancer chemopreventive agents. Recently we demonstrated that fully methylated flavones have greatly increased metabolic stability and intestinal transport. However, their effects on cancer cell proliferation are not well understood. In the present study we compared the effects of fully methylated versus unmethylated flavones on oral cancer cell proliferation, using BrdU incorporation into newly synthesized DNA as the assay. In the human oral SCC‐9 cancer cells, 5,7‐dimethoxyflavone and 5,7,4′‐trimethoxyflavone were ten times more potent inhibitors of cell proliferation (IC 50 5–8 μM) than the corresponding unmethylated analogs chrysin and apigenin. Several other methylated flavones also inhibited cell proliferation but were less potent. Cell cycle analysis showed that both 5,7‐dimethoxyflavone and 5,7,4′‐trimethoxyflavone arrested the SCC‐9 cells in G1 phase with a concomitant decrease in S phase, dramatically different from the unmethylated analogs which promoted G2/M arrest. Both methylated compounds inhibited the proliferation of two other cancer cell lines but had very poor effectiveness in two immortalized normal cell lines. Thus, some bioavailable, fully methylated flavones appear to have great potential as cancer chemopreventive/chemotherapeutic agents. Supported by NIH grant GM55561.