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 signaling 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 the PMA treatment group. In addition, lapachol increased
the expression level of TIMP-1 compared with the PMA treatment group. Moreover, lapachol decreased
the expression level of p-p38 among MAPKs compared with the 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 the 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 in TIMP-1 expression as well as the inactivation of
p38 through NF-kB transcription factor.