Background:
Anti-cancer effect of lapachol contained in Tabebuia avellandae has been poorly understood until
now.
Objective:
The aim of this study was to investigate the inhibitory effect of lapachol on MMPs related to cell invasion. Its
action mechanism was elucidated by analyzing the activity and the expression of MMPs and the proteins involved in the
signalling pathway of cell invasion.
Methods:
The cytotoxicity of lapachol was evaluated by MTT assay in HT1080 cells. The effects of lapachol on the
expression and the activation of MMPs were analyzed by western blot, immunofluorescence staining and gelatin
zymography assays. Their gene expression was analyzed by RT-PCR, and metastasis was evaluated by cell invasion
assay.
Results:
Lapachol below 2 µM showed no cytotoxicity. It was observed that lapachol above 0.5 µM inhibited the
activation of MMP-2 and MMP-9 stimulated by PMA. In particular, the protein and gene expression levels of MMP-2
stimulated by PMA were remarkably decreased in the presence of lapachol at 1 µM compared with PMA treatment group.
In addition, lapachol increased the expression level of TIMP-1 compared with PMA treatment group. Moreover, lapachol
decreased the expression level of p-p38 among MAPKs compared with PMA treatment group. It was also found that the
expression level of p65, a part of NF-kB, in nuclei was reduced in the presence of lapachol above 0.5 µM compared with
PMA treatment group. In addition, lapachol inhibited the invasion of human fibrosarcoma cells stimulated with VEGF.
Conclusion:
Above results suggest that lapachol could play an important role in the modulation of MMPs related to cell
invasion via the increase of TIMP-1 expression as well as the inactivation of p38 through NF-kB transcription factor.