Acacetin, a flavonoid, inhibits the invasion and migration of human prostate cancer DU145 cells via inactivation of the p38 MAPK signaling pathway.
Acacetin (5,7-dihydroxy-4'-methoxyflavone), a flavonoid compound, has anti-peroxidative and anti-inflammatory effects. The effect of acacetin on antimetastasis in human prostate cancer DU-145 cells was investigated. First, the result demonstrated acacetin could exhibit an inhibitory effect on the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay, wound-healing assay, and Boyden chamber assay. Data also showed acacetin could inhibit the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) involved in the downregulation of the expressions of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-type plasminogen activator (u-PA) at both the protein and mRNA levels. Next, acacetin significantly decreased the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun. Also, the treatment with acacetin to DU145 cells also leads to a dose-dependent inhibition on the binding ability of NF-kappaB and activator protein-1 (AP-1). Furthermore, the treatment of inhibitors specific for p38 MAPK (SB203580) to DU145 cells could cause reduced expressions of MMP-2, MMP-9, and u-PA. These results showed acacetin could inhibit the invasion and migration abilities of DU145 cells by reducing MMP-2, MMP-9, and u-PA expressions through suppressing p38 MAPK signaling pathway and inhibiting NF-kappaB- or AP-1-binding activity. These findings proved acacetin might be offered further application as an antimetastatic agent.
Shen
Kun-Hung
KH
Division of Urology, Department of Surgery, Chi Mei Medical Center, Tainan, 710, Taiwan.
Hung
Shun-Hsing
SH
Yin
Li-Te
LT
Huang
Chun-Shui
CS
Chao
Chang-Hung
CH
Liu
Chein-Liang
CL
Shih
Yuan-Wei
YW
D000970:Antineoplastic Agents; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D047309:Flavones / Q000494:pharmacology* / Q000627:therapeutic use; D005419:Flavonoids; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000517:prevention & control; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger; D015398:Signal Transduction / Q000187:drug effects*; D014568:Urokinase-Type Plasminogen Activator; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects*
D000970:Antineoplastic Agents; D047309:Flavones; D005419:Flavonoids; D012333:RNA, Messenger; D048051:p38 Mitogen-Activated Protein Kinases; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases; C023717:acacetin
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