Raf and PI3K are the Molecular Targets for the Anti‐metastatic Effect of Luteolin. (21st November 2012)

• Record Type: Journal Article
• Authors: Kim, Ho Young; Jung, Sung Keun; Byun, Sanguine; Son, Joe Eun; Oh, Mi Hyun; Lee, Jihoon; Kang, Min Jeong; Heo, Yong‐Seok; Lee, Ki Won; Lee, Hyong Joo
• Is Part Of: Phytotherapy research. Volume 27:Number 10(2013:Oct.)
• Page Start: 1481
• Page End: 1488
• Publication Date: 2012-11-21
• Subjects: Materia medica, Vegetable -- Periodicals; Botany, Medical -- Periodicals; Medicinal plants -- Periodicals; Plant Extracts -- therapeutic use -- Periodicals; Plants, Medicinal -- Periodicals; 581.634
• DOI: 10.1002/ptr.4888
• Languages: English
• ISSNs: 0951-418X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Metastases are the primary cause of human cancer deaths. Luteolin, a naturally occurring phytochemical, has chemopreventive and/or anticancer properties in several cancer cell lines. However, anti‐metastatic effects of luteolin <italic>in vivo</italic> and the underlying molecular mechanisms and target(s) remain unknown. Luteolin suppresses matrix metalloproteinase (MMP)‐2 and ‐9 activities and invasion in murine colorectal cancer CT‐26 cells. Western blot and kinase assay data revealed that luteolin inhibited Raf and phosphatidylinositol 3‐kinase (PI3K) activities and subsequently attenuated phosphorylation of MEK and Akt. A pull‐down assay indicated that luteolin non‐competitively bound with ATP to suppress Raf activity and competitively bound with ATP to inhibit PI3K activity. GW5074, a Raf inhibitor, and LY294002, a PI3K inhibitor, inhibited MMP‐2 and ‐9 activities and invasion in CT‐26 cells. An <italic>in vivo</italic> mouse study showed that oral administration (10 or 50 mg/kg) of luteolin significantly inhibited tumor nodules and tumor volume of lung metastasis induced by intravenous injection of CT‐26 cells. Luteolin also inhibited MMP‐9 expression and activity in CT‐26‐induced mouse lung tissue. These results suggest that luteolin may have considerable potential for development as an anti‐metastatic agent. Copyright © 2012 John Wiley &amp; Sons, Ltd.</p> </abstract>