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Actinidia callosa var. callosa suppresses metastatic potential of human hepatoma cell SK-Hep1 by inhibiting matrix metalloproteinase-2 through PI3K/Akt and MAPK signaling pathways

Deng, Jeng-Shyan, Chang, Jui-Shu, Liao, Jung-Chun, Chao, Wei, Lee, Ming-Ming, Cheng, Chien-Hua, Huang, Guan-Jhong
Botanical studies 2018 v.59 no.1 pp. 3
Actinidia, Western blotting, casein, cytotoxicity, dose response, ethyl acetate, gelatin, gelatinase A, hepatoma, humans, metastasis, mitogen-activated protein kinase, mortality, non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase, phosphorylation, signal transduction, threonine
BACKGROUND: Cancer cell metastasis involving multi-step procedures and cytophysiological property changes may make difficult in the clinical management and death rate increasing. RESULTS: In this study, we first observed that ethyl acetate fraction of Actinidia callosa var. callosa (EAAC) carry out a dose-dependent inhibitory effect without cytotoxicity on the mobility and invasion of highly metastatic SK-Hep1 cells. To investigate the EAAC in cancer metastasis, SK-Hep1 cells were treated with EAAC at various concentrations and then subjected to gelatin zymography, casein zymography and western blot to study the impacts of EAAC on metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1/2 (TIMP-1/2), respectively. Our results showed that EAAC treatment may decrease the expressions of MMP-2 and enhance the expression of TIMP-1/2 in a concentration-dependent manner. EAAC also inhibited effect on the phosphorylation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase/serine/threonine protein kinase [or protein kinase B (PI3K/Akt)] and focal adhesion kinase (FAK). CONCLUSIONS: These results indicate that EAAC inhibited SK-Hep1 cell of metastasis by reduced protein level of MMP-2 through the suppression of MAPK and FAK signaling pathway and of the activity of PI3K/Akt. These findings suggest that EAAC may be used as an antimetastatic agent.