Minocycline is More Potent Than Tetracycline and Doxycycline in Inhibiting MMP-9 in Vitro

Abstract

Background: Tetracyclines are antimicrobial agents that possess anti-inflammatory and matrix metalloproteinase (MMP) inhibitory effects. Tetracycline, doxycycline, and minocycline have shown different potencies in inhibiting various MMPs. MMPs are a conserved family of zinc-dependent endopeptidases, which are involved in various physiologic and pathologic conditions. MMP-9 is among the most important proteases involved in the development of cardiovascular disease, cancer, and inflammatory disease Objectives: Considering the central role of MMP-9 in the above-mentioned diseases and the variable inhibitory potentials of routine tetracyclines, including tetracycline, doxycycline, and minocycline, this study measured the inhibitory effect of these routine tetracycline agents on MMP-9 activity obtained from U-937 cell cultures using the zymography method. Materials and Methods: An MMP-9-rich culture medium of U-937 cells was used as the source of the enzyme. Serial dilutions of 5, 20,

Oxaprozin: A new hope in the modulation of matrix metalloproteinase 9 activity

“…The IC 50 value sounds particularly interesting if compared to those obtained by Modheji, Olapour, Khodayar, Jalili, and Yaghooti (2016) who evaluated the inhibition of MMP-9 by several tetracyclines, antimicrobial agents showing a wellknown MMP inhibitory effects. Among these, the best inhibitor was identified in minocycline with an IC 50 of 10.7 μM in the presence of MMP-9 produced by U-937 cells (Modheji et al, 2016). Double reciprocal plots of 1/V versus 1/[S] (Figure 3a), obtained by using increasing substrate (from 0.375 to 1.5 μM) in combination with different concentrations of oxaprozin (from 0 to 50 μM), showed a mechanism of competitive inhibition and the K app m values were calculated with the aim to draw a secondary plot (Figure 3b) for the determination of K i , which was equal to 7.23 ± 0.43 μM.…”

“…The use of a constant concentration of substrate (3.3 μM), in the presence of increasing concentrations of oxaprozin (range 0-100 μM), was useful to define the IC 50 which is equal to 22.73 ± 1.93 μM. The IC 50 value sounds particularly interesting if compared to those obtained by Modheji, Olapour, Khodayar, Jalili, and Yaghooti (2016) who evaluated the inhibition of MMP-9 by several tetracyclines, antimicrobial agents showing a wellknown MMP inhibitory effects. Among these, the best inhibitor was identified in minocycline with an IC 50 of 10.7 μM in the presence of MMP-9 produced by U-937 cells (Modheji et al, 2016).…”

Selective toxicity of antibacterial agents—still a valid concept or do we miss chances and ignore risks?

“…Three examples should be mentioned pars pro toto: azithromycin and moxifloxacin decreased respiratory epithelial cell derived MMP1 and -3 concentrations, whereas both agents increased MMP secretion from MRC-5 fibroblasts [ 44 ]. Concentrations of doxycycline to inhibit MMP-9 synthesis to 50% (IC 50 ) ranged in different cell lines from 1 to 608 μM [ 43 , 45 ]. IC 50 -values of azithromycin for inhibition of proliferation and induction of apoptosis in HeLa-, cervical- and gastric cancer cells were 15.66, 26.05 and 91.00 mg/L [ 46 ].…”

Minocycline in Treating Glioblastoma Multiforme: Far beyond a Conventional Antibiotic

“…Matrix metalloproteinases (MMPs) have been identified as the main proteolytic enzymes used to regulate the degradation of the extracellular matrix (ECM) [ 27 ]. It has been shown that tetracyclines and chemically modified tetracyclines, especially minocycline, suppress the activity of several MMPs [ 28 ], to induce cell growth suppression in numerous cancer cells. Masumori et al have shown that minocycline could inhibit invasion and pulmonary metastasis, both in vitro and in vivo [ 29 ].…”