Potent selective inhibition of MMP-14 by chloroauric acid and its inhibitory effect on cancer cell invasion

Abstract

Matrix metalloproteinases (MMPs) are a family of zinc-containing proteases with vital roles in extracellular matrix remodeling. The regulation of MMPs can modulate a number of cellular activities. The therapeutic potential of MMP inhibitors has been shown for diseases such as arthritis and cancer. This paper is the first to demonstrate that HAuCl₄ inhibits the activity of MMP-2 and MMP-13 as well as having a more specific inhibitory effect on MMP-14. The effect of HAuCl₄ on MMP-14 involves a non-competitive reversible inhibitory mechanism. Moreover, 0–50 μM HAuCl₄ did not affect the cell viability of HT-1080 human fibrosarcoma cells. However, HAuCl₄ at these concentrations showed significant inhibitory effects on the invasion of the HT-1080 cells, thereby suggesting that HAuCl₄ may modulate tumor cell behaviors by inhibiting MMP-14. These findings provide initial clues to further elucidate the biological activity of HAuCl₄ and its potential therapeutic value for related diseases.