Apigenin and luteolin bind MMP2 and MMP9 proteins while showing potential activity against breast cancer cell lines, presenting dual targeting mechanisms.
LC–ESI–MS/MS Investigation Identifies 28 Compounds in the Extract
The LC–ESI–MS/MS investigation of the extract identified 28 compounds categorized into organic acids, phenolics, flavonoids, sesquiterpenes, sterols, and fatty acids. Major compounds included apigenin at 12.99%, medioresinol at 8.32%, and luteolin at 8.32%. Molecular docking revealed that luteolin exhibits the strongest predicted affinity for MMP2 at -8.90 kcal/mol and MMP9 at -9.50 kcal/mol.
Saussurea Costus Root Extract Contains Flavonoids and Shows Cytotoxicity
- Saussurea costus root extract contains major flavonoids including apigenin, medioresinol, and luteolin.
- Medioresinol demonstrates strong predicted affinity for MMP2 mRNA at -67.266 kcal/mol and MMP9 mRNA at -80.999 kcal/mol.
- The extract exhibits dose-dependent cytotoxicity against the MCF7 breast cancer cell line with an IC50 value of 106.8 ± 1.43 μg/mL.
Flavonoids Show High Predicted Affinity for MMP2 and MMP9
Flavonoids generally exhibited higher predicted affinity, with luteolin showing the most favorable calculated binding energies for MMP2 and MMP9. For MMP2, apigenin-7-O-glucoside recorded the most favorable calculated binding energy at -9.10 kcal/mol. Organic acids, fatty acids, and sterols showed moderate to weak binding ranging from -4.50 to -7.80 kcal/mol, with malic acid showing the weakest calculated affinity.
All three tested ligands showed strong predicted binding to both mRNAs, with free energies ranging from -51.072 to -80.999 kcal/mol. Medioresinol showed the most favorable predicted affinity for MMP2 and MMP9 mRNAs, forming multiple hydrogen bonds with residues such as G605, U704, C707, C708, and A1735 in MMP2.
Luteolin and Apigenin-7-O-Glucoside Interact with Target Proteins
| Compound | Target Protein | Binding Energy (kcal/mol) | Key Interactions |
|---|---|---|---|
| Luteolin | MMP2 | -8.90 | Dynamic hydrogen bonds, RMSD stabilization |
| Luteolin | MMP9 | -9.50 | Weak hydrogen bonds, non-polar interactions |
| Apigenin-7-O-glucoside | MMP2 | -9.10 | High predicted affinity |
Hydrogen bonding between luteolin and MMP2 is dynamic, with the average number of hydrogen bonds per frame measuring about 0.9 to 1.1. After approximately 20 ns, MMP2 stabilizes around an RMSD of 0.42 nm, while the MMP2-luteolin complex stabilizes at 0.45 to 0.55 nm. The solvent accessible surface area of the luteolin-MMP2 complex decreased from approximately 90.1 nm2 to 86.9 nm2 over 100 ns of molecular dynamics simulation.
For the MMP9 molecular dynamics simulation with luteolin, hydrogen bonds remained weak and transient throughout the trajectory. The RMSD analysis confirmed stability and equilibration, settling into a range of 0.28 to 0.32 nm after a 0 to 20 ns relaxation period. The radius of gyration of the MMP9-luteolin complex fluctuated in a narrow range of approximately 1.43 nm to 1.48 nm.
Cytotoxicity Against Breast Cancer Cells
The experimental evaluation of anticancer effects demonstrated that the extract exhibited an IC50 value of 106.8 ± 1.43 μg/mL against the MCF7 cell line. The half-maximal inhibitory concentration concentrations used for all subsequent functional assays were established at 53 µg/mL for the extract and 53 µg/mL for doxorubicin against MCF7 cells.
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