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Andrographolide could inhibit human colorectal carcinoma Lovo cells migration and invasion via down-regulation of MMP-7 expression
Authors:Ming-Der Shi   Hui-Hsuan Lin   Tai-An Chiang   Li-Yu Tsai   Shu-Mei Tsai   Yi-Chieh Lee  Jing-Hsien Chen  
Affiliation:a Pathology and Laboratory Medicine, Yongkang Veterans Hospital, Tainan, Taiwan
b Department of Medical Laboratory and Biotechnology Science, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan
c School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan
d Department of Medical Technology and Graduate Institute of Biological Science and Technology, College of Medicine and Life Science, Chung Hwa University of Medical Technology, No. 89, Wen Hwa 1st St., Rende Shiang, Tainan County 717, Taiwan
e Department of Biological Science and Technology and Institute of Biomedical Science, College of Medicine and Life Science, Chung Hwa University of Medical Technology, Tainan, Taiwan
Abstract:Andrographolide (Andro), a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, is known to possess multiple pharmacological activities. In our previous study, Andro had been shown to have potent anti-cancer activity against human colorectal carcinoma Lovo cells by inhibiting cell-cycle progression. To further investigate the mechanism for the anti-cancer properties of Andro, it was used to examine the effect on migration and invasion of Lovo cells. The results of wound-healing assay and in vitro transwell assay revealed that Andro inhibited dose-dependently the migration and invasion of Lovo cells under non-cytotoxic concentrations. Using zymographic assay and RT-PCR, the results revealed that Andro diminished the activity and the mRNA and protein levels of MMP-7, but not MMP-2 or MMP-9. The down-regulation of MMP-7 appeared to be via the inactivation of activator protein-1 (AP-1) since the treatment with Andro suppressed the nuclear protein level of AP-1, which was accompanied by a decrease in DNA-binding level of the factor. Taken together, these results indicated that Andro reduces the MMP-7-mediated cellular events in Lovo cells, and provided a new mechanism for its anti-cancer activity.
Keywords:Andrographolide   Human colorectal carcinoma   Migration   Invasion   Metalloproteinase
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