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Decursin and Decursinol from Angelica gigas Inhibit the Lung Metastasis of Murine Colon Carcinoma
Author(s) -
Son Seung Hwa,
Park KwangKyun,
Park Sun Kyu,
Kim Young Choong,
Kim Yeong Shik,
Lee SangKook,
Chung WonYoon
Publication year - 2011
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.3372
Subject(s) - medicine , kinase , matrix metalloproteinase , mapk/erk pathway , cell growth , metastasis , metalloproteinase , cell culture , cancer research , pharmacology , biochemistry , cancer , chemistry , biology , genetics
The principal objective of the present study was to evaluate the antimetastatic activity of decursin and decursinol isolated from Angelica gigas . Decursin and decursinol inhibited the proliferation and invasion of CT‐26 colon carcinoma cells. The expressions of matrix metalloproteinase (MMP)‐2 and MMP‐9 in cells and the activities in the culture medium were also reduced by decursin and decursinol treatment. In CT‐26 cells, the extracellular signal‐regulated kinase (ERK) inhibitor inhibited cell proliferation, invasion and MMP‐9 expression, and the c‐Jun N ‐terminal kinase (JNK) inhibitor suppressed the expression of both MMPs, as well as cell proliferation and cell invasion. The phosphatidylinositol‐3 kinase (PI3K) inhibitor reduced only the expression of MMP‐2. In addition, the invasion of CT‐26 cells was inhibited by the treatment with anti‐MMP‐9 antibody, rather than anti‐MMP‐2 antibody. These results indicate that MMP‐9 expression via ERK and JNK plays a critical role for the invasion of CT26 cells. Decursin and decursinol downregulated ERK and JNK phosphorylation. Moreover, oral administration of decursin and decursinol reduced the formation of tumor nodules in the lungs and the increase in lung weight caused by CT‐26 metastases. Therefore, both decursin and decursinol may be benefi cial antimetastatic agents, targeting MMPs and their upstream signaling molecules. Copyright © 2011 John Wiley & Sons, Ltd.