Andrographolide could inhibit human colorectal carcinoma Lovo cells migration and invasion via down-regulation of MMP-7 expression.
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.
Shi
Ming-Der
MD
Pathology and Laboratory Medicine, Yongkang Veterans Hospital, Tainan, Taiwan.
Lin
Hui-Hsuan
HH
Chiang
Tai-An
TA
Tsai
Li-Yu
LY
Tsai
Shu-Mei
SM
Lee
Yi-Chieh
YC
Chen
Jing-Hsien
JH
D035685:Andrographis / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation; D029001:Herbal Medicine; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004224:Diterpenes; D018808:Transcription Factor AP-1; C030419:andrographolide; D020783:Matrix Metalloproteinase 7