Related Experiment Video
Updated: Aug 28, 2025
Measuring Global Cellular Matrix Metalloproteinase and Metabolic Activity in 3D Hydrogels
Published on: January 22, 2019
Discovery of Phenolic Matrix Metalloproteinase Inhibitors by Peptide Microarray for Osteosarcoma Treatment
Minghong Jian1,2, Xudong Sun1,2, Guorong Cheng2,3
1State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.
Abstract:
Because of the abnormal upregulation of matrix metalloproteinase (MMP) activities in tumors, MMP inhibitors (MMPIs) are validated anticancer drug candidates. We identified several MMPIs including mangiferin as an MMP-9 inhibitor with a half maximal inhibitory concentration (IC50) value of 250 nM, isosilybin as an MMP-13 inhibitor with an IC50 value of 250 nM, and isoliquiritigenin as a broad-spectrum MMPI (with IC50 values of 16 nM for MMP-1, 10 nM for MMP-2, 81 nM for MMP-3, 8 nM for MMP-7, 10 nM for MMP-9, and 14 nM for MMP-13) through studying the interactions of 6 MMPs secreted by U-2OS cells with 51 phenolic natural products on the peptide microarray platform. In addition, the inhibitory mechanisms of as-discovered MMPIs were evaluated by a molecular docking simulation. The antitumor efficiencies of MMPIs were demonstrated by both a cell scratch test and growth suppression of mouse-born OS tumors. The results of the cell scratch test suggested that isoliquiritigenin significantly inhibited the migration of U-2OS cells. In addition, administration of isoliquiritigenin significantly reduced the tumor size (by about 80%) and prolonged the survival time (by more than 70 days). This study suggests that the discovery of MMPIs from phenolic natural products is a meaningful way to screen anticancer agents.
Insights
Natural compounds like isoliquiritigenin show promise as anticancer drugs by inhibiting matrix metalloproteinase (MMP) activity. These MMP inhibitors (MMPIs) effectively suppressed tumor growth and migration in preclinical models.
Area of Science:
- Biochemistry
- Pharmacology
- Oncology
Background:
- Matrix metalloproteinase (MMP) activity is abnormally upregulated in tumors, making MMP inhibitors (MMPIs) promising anticancer drug candidates.
- Phenolic natural products represent a potential source for novel MMPIs.
Purpose of the Study:
- To identify and characterize novel MMP inhibitors (MMPIs) from phenolic natural products.
- To evaluate the antitumor efficacy of identified MMPIs in preclinical models.
Main Methods:
- Screening of 51 phenolic natural products against 6 MMPs using a peptide microarray platform.
- Evaluation of inhibitory mechanisms via molecular docking simulations.
- Assessment of antitumor activity using cell scratch assays and in vivo tumor growth suppression in mice.
Main Results:
- Identified several MMPIs, including mangiferin (MMP-9 inhibitor), isosilybin (MMP-13 inhibitor), and isoliquiritigenin (broad-spectrum MMPI).
- Isoliquiritigenin demonstrated significant inhibition of U-2OS cell migration.
- Isoliquiritigenin administration reduced tumor size by approximately 80% and extended survival by over 70 days in mouse models.
Conclusions:
- Phenolic natural products are a valuable resource for discovering effective anticancer agents like MMPIs.
- Isoliquiritigenin shows significant potential as an anticancer therapeutic due to its MMP inhibitory activity and demonstrated antitumor effects.
