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

被引:38
作者
Fong, Yaou [1 ]
Shen, Kun-Hung [2 ,3 ,4 ]
Chiang, Tai-An [5 ,6 ]
Shih, Yuan-Wei
机构
[1] Chi Mei Med Ctr, Dept Surg, Div Thorac Surg, Tainan, Taiwan
[2] Chi Mei Med Ctr, Dept Surg, Div Urol, Tainan, Taiwan
[3] Chia Nan Univ Pharm & Sci, Dept Childhood Educ & Nursery, Tainan, Taiwan
[4] Taipei Med Univ, Dept Urol, Taipei, Taiwan
[5] Chung Hwa Univ Med Technol, Dept Med Technol, Tainan, Taiwan
[6] Chung Hwa Univ Med Technol, Grad Inst Biol Sci & Technol, Tainan, Taiwan
关键词
acacetin; invasion; JNK; migration; MMP-2; u-PA; UROKINASE-PLASMINOGEN-ACTIVATOR; MATRIX METALLOPROTEINASES; CYCLE PROGRESSION; INVASION; APOPTOSIS; KINASE; GROWTH; PROLIFERATION;
D O I
10.1111/j.1750-3841.2009.01438.x
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
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-kappa B), c-Fos, and c-Jun. Also, a dose-dependent inhibition on the binding abilities of NF-kappa B and activator protein-1 (AP-1) by acacetin treatment was further observed. Further, the treatment of specific inhibitor for INK (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 INK and reducing NF-kappa B and AP-1 binding activities.
引用
收藏
页码:H30 / H38
页数:9
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