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Acacetin Inhibits TPA‐Induced MMP‐2 and u‐PA Expressions of Human Lung Cancer Cells Through Inactivating JNK Signaling Pathway and Reducing Binding Activities of NF‐κB and AP‐1
Author(s) -
Fong Yaou,
Shen KunHung,
Chiang TaiAn,
Shih YuanWei
Publication year - 2010
Publication title -
journal of food science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.772
H-Index - 150
eISSN - 1750-3841
pISSN - 0022-1147
DOI - 10.1111/j.1750-3841.2009.01438.x
Subject(s) - acacetin , chemistry , phosphorylation , activator (genetics) , a549 cell , cancer research , kinase , nf κb , microbiology and biotechnology , signal transduction , biochemistry , cell , biology , flavonoid , receptor , apigenin , antioxidant
ABSTRACT: Acacetin (5,7‐dihydroxy‐4′‐methoxyflavone), a flavonoid compound, has antiperoxidative and antiinflammatory effects. The effect of acacetin on 12‐ O ‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced MMPs and u‐PA expressions in human lung cancer A549 cells was investigated. First, the result demonstrated acacetin could inhibit TPA‐induced the abilities of the adhesion, invasion, and migration by cell‐matrix adhesion assay and Boyden chamber assay. Data also showed acacetin could inhibit phosphorylation of c‐Jun N‐terminal kinase 1 and 2 (JNK1/2) involved in the down‐regulating protein expressions and transcriptions of matrix metalloproteinase‐2 (MMP‐2) and urokinase‐type plasminogen activator (u‐PA) induced by TPA. Next, acacetin also strongly inhibited TPA‐stimulated the nuclear levels of nuclear factor kappa B (NF‐κB), c‐Fos, and c‐Jun. Also, a dose‐dependent inhibition on the binding abilities of NF‐κB and activator protein‐1 (AP‐1) by acacetin treatment was further observed. Further, the treatment of specific inhibitor for JNK (SP600125) to A549 cells could inhibit TPA‐induced MMP‐2 and u‐PA expressions along with an inhibition on cell invasion and migration. Taken together, these results suggest the antimetastatic effects of acacetin on the TPA‐induced A549 cells might be by reducing MMP‐2 and u‐PA expressions through inhibiting phosphorylation of JNK and reducing NF‐κB and AP‐1 binding activities.