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Cucurbitacin B inhibits 12‐O‐tetradecanoylphorbol 13‐acetate‐induced invasion and migration of human hepatoma cells through inactivating mitogen‐activated protein kinase and PI3K/Akt signal transduction pathways
Author(s) -
Zhou Xueying,
Yang Jiao,
Wang Yanli,
Li Wen,
LiLing Jesse,
Deng Yihui,
Zhang Meixia
Publication year - 2012
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2011.00933.x
Subject(s) - protein kinase b , 12 o tetradecanoylphorbol 13 acetate , mapk/erk pathway , pi3k/akt/mtor pathway , kinase , signal transduction , cell migration , p38 mitogen activated protein kinases , protein kinase a , cancer research , microbiology and biotechnology , chemistry , biology , protein kinase c , cell , biochemistry , phorbol ester
Aim: Cucurbitacin B (CuB) is an active component isolated from various plants used as folk medicine in Asian countries and has shown diverse antitumor activities. There is, however, no documented effect of CuB on the migration and invasion of human hepatoma cells yet. The purpose of this study was to assess the effect of CuB on the migration and invasion of hepatoma cells and to explore the possible mechanism. Methods: Human hepatoma cell lines HepG2 and BEL‐7402 were used for the study. Effects of CuB on cancer cell migration and invasion were evaluated in vitro with wound healing and transwell assays. The effect of CuB on the expression of matrix metalloproteinase (MMP)‐9, mitogen‐activated protein kinases (MAPKs), Akt, nuclear factor‐κB (NF‐κB), c‐Fos and c‐Jun was investigated with gelatin zymography and/or western blotting. Results: Cucurbitacin B has significantly suppressed 12‐O‐tetradecanoylphorbol 13‐acetate (TPA)‐induced cell invasion and migration in a concentration‐dependent manner, which was accompanied with suppression of TPA‐induced MMP‐9 expression through inactivation of phosphorylation of extracellular signal‐regulated kinase (ERK) 1/2, p38 and Akt. In the nucleus, it has also strongly suppressed TPA‐stimulated expression of NF‐κB, c‐Jun and c‐Fos. Conclusion: Cucurbitacin B has a potential value for suppressing metastasis of human hepatoma cells through suppressing the expression of MMP‐9.