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: Kun-Hung Shen, Shun-Hsing Hung, Li-Te Yin, Chun-Shui Huang, Chang-Hung Chao, Chein-Liang Liu, Yuan-Wei Shih
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 333 Issue 1-2 Pg. 279-91 (Jan 2010) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 19693651 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Flavones
• Flavonoids
• RNA, Messenger
• p38 Mitogen-Activated Protein Kinases
• Urokinase-Type Plasminogen Activator
• Matrix Metalloproteinases
• acacetin

Topics

• Antineoplastic Agents
• Cell Line, Tumor
• Cell Movement (drug effects)
• Flavones (pharmacology, therapeutic use)
• Flavonoids
• Humans
• Male
• Matrix Metalloproteinases
• Neoplasm Invasiveness (prevention & control)
• Neoplasm Metastasis (drug therapy, prevention & control)
• Phosphorylation
• Prostatic Neoplasms (drug therapy, metabolism, pathology)
• RNA, Messenger
• Signal Transduction (drug effects)
• Urokinase-Type Plasminogen Activator
• p38 Mitogen-Activated Protein Kinases (drug effects)