Raf and PI3K are the molecular targets for the anti-metastatic effect of luteolin

Ho Young Kim, Sung Keun Jung, Sanguine Byun, Joe Eun Son, Mi Hyun Oh, Jihoon Lee, Min Jeong Kang, Yong Seok Heo, Ki Won Lee, Hyong Joo Lee

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22 Citations (Scopus)

Abstract

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 in vivo 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 in vivo 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.

Original languageEnglish
Pages (from-to)1481-1488
Number of pages8
JournalPhytotherapy Research
Volume27
Issue number10
DOIs
Publication statusPublished - 2013 Oct

All Science Journal Classification (ASJC) codes

  • Pharmacology

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    Kim, H. Y., Jung, S. K., Byun, S., Son, J. E., Oh, M. H., Lee, J., Kang, M. J., Heo, Y. S., Lee, K. W., & Lee, H. J. (2013). Raf and PI3K are the molecular targets for the anti-metastatic effect of luteolin. Phytotherapy Research, 27(10), 1481-1488. https://doi.org/10.1002/ptr.4888