title: Acacetin, a flavonoid, inhibits the invasion and migration of human prostate cancer DU145 cells via inactivation of the p38 MAPK signaling pathway.
abstract: 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.
authors.affiliation: Division of Urology, Department of Surgery, Chi Mei Medical Center, Tainan, 710, Taiwan.
authors.forename: Kun-Hung
authors.initials: KH
authors.lastname: Shen
authors.forename: Shun-Hsing
authors.initials: SH
authors.lastname: Hung
authors.forename: Li-Te
authors.initials: LT
authors.lastname: Yin
authors.forename: Chun-Shui
authors.initials: CS
authors.lastname: Huang
authors.forename: Chang-Hung
authors.initials: CH
authors.lastname: Chao
authors.forename: Chein-Liang
authors.initials: CL
authors.lastname: Liu
authors.forename: Yuan-Wei
authors.initials: YW
authors.lastname: Shih
mesh_terms: 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*
chemical_list: 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
references.citation: J Agric Food Chem. 2005 Feb 9;53(3):620-30
references.pmid: 15686411
references.citation: Curr Cancer Drug Targets. 2004 Jun;4(4):327-36
references.pmid: 15180498
references.citation: Annu Rev Cell Biol. 1993;9:541-73
references.pmid: 8280471
references.citation: Cancer Lett. 2008 Oct 8;269(2):199-225
references.pmid: 18479807
references.citation: Biochem Pharmacol. 2006 Nov 15;72(10):1293-303
references.pmid: 16949556
references.citation: J Nutr Biochem. 2009 Sep;20(9):663-76
references.pmid: 18824345
references.citation: Chem Biol Interact. 2005 Oct 20;156(2-3):141-50
references.pmid: 16169542
references.citation: Nucleic Acids Res. 1991 Sep 25;19(18):5080
references.pmid: 1717940
references.citation: Clin Biochem. 2004 Jul;37(7):541-8
references.pmid: 15234235
references.citation: J Biol Chem. 1999 Jul 30;274(31):21491-4
references.pmid: 10419448
references.citation: FASEB J. 1999 May;13(8):781-92
references.pmid: 10224222
references.citation: Biochem Pharmacol. 2005 Jan 15;69(2):221-32
references.pmid: 15627474
references.citation: Mol Cells. 2007 Aug 31;24(1):95-104
references.pmid: 17846503
references.citation: J Natl Cancer Inst. 1997 May 21;89(10):689-96
references.pmid: 9168183
references.citation: Carcinogenesis. 2005 Apr;26(4):845-54
references.pmid: 15637089
references.citation: J Mol Cell Cardiol. 2007 Aug;43(2):168-76
references.pmid: 17560598
references.citation: Nat Rev Cancer. 2002 Apr;2(4):289-300
references.pmid: 12001990
references.citation: Cancer Res. 2005 Feb 1;65(3):1035-44
references.pmid: 15705905
references.citation: Cancer Lett. 2004 Aug 20;212(1):53-60
references.pmid: 15246561
references.citation: Int J Mol Med. 2008 May;21(5):577-84
references.pmid: 18425349
references.citation: J Ethnopharmacol. 2008 Oct 30;120(1):1-6
references.pmid: 18721870
references.citation: Biochem J. 1998 Dec 15;336 ( Pt 3):599-609
references.pmid: 9841871
references.citation: CA Cancer J Clin. 2000 Jan-Feb;50(1):7-33
references.pmid: 10735013
references.citation: Proc Natl Acad Sci U S A. 1994 May 10;91(10):4293-7
references.pmid: 8183903
references.citation: Nat Rev Cancer. 2003 Jul;3(7):489-501
references.pmid: 12835669
references.citation: Biochem Biophys Res Commun. 2007 Mar 2;354(1):165-71
references.pmid: 17214970
references.citation: J Biol Chem. 1996 May 3;271(18):10672-80
references.pmid: 8631874
references.citation: FASEB J. 2001 Sep;15(11):1953-62
references.pmid: 11532975
references.citation: Cancer Chemother Pharmacol. 1999;43 Suppl:S42-51
references.pmid: 10357558
references.citation: Adv Cancer Res. 1990;54:159-211
references.pmid: 1688681
references.citation: Phytother Res. 2003 Feb;17(2):123-8
references.pmid: 12601673
references.citation: Essays Biochem. 2002;38:21-36
references.pmid: 12463159
references.citation: Biochem Pharmacol. 2004 Mar 1;67(5):823-9
references.pmid: 15104235
references.citation: Hum Gene Ther. 2009 Apr;20(4):361-73
references.pmid: 19199789
references.citation: J Agric Food Chem. 2009 Feb 25;57(4):1291-8
references.pmid: 19178296
references.citation: Cell Mol Life Sci. 2004 Jan;61(1):118-28
references.pmid: 14704859
references.citation: Int Immunopharmacol. 2008 Dec 20;8(13-14):1821-6
references.pmid: 18801463