Computational Insights into Captopril's Inhibitory Potential Against MMP9 and LCN2 in Bladder Cancer: Implications...

Area of Science:

• Oncology
• Pharmacology
• Biochemistry

Background:

• Captopril is a widely used medication for hypertension and heart failure.
• Proteins MMP9 and LCN2 are significantly associated with bladder cancer (BLCA) progression and reduced patient survival.
• There is a need for novel therapeutic strategies for BLCA, particularly for patients with co-existing hypertension.

Purpose of the Study:

• To investigate the potential of captopril as a therapeutic agent for bladder cancer (BLCA).
• To identify and analyze the direct protein targets of captopril associated with BLCA.
• To evaluate the inhibitory effects of captopril on overexpressed proteins in BLCA.

Main Methods:

• Utilized DrugBank 5.0 for identifying captopril's direct protein targets (DPTs).
• Employed STRING for protein-protein interaction analysis and TNMPlot for gene expression comparison.
• Performed molecular docking and molecular dynamics simulations to analyze captopril's interaction with target proteins.

Main Results:

• Identified MMP9 as an overexpressed gene in BLCA, with captopril effectively inhibiting both wild-type and mutated forms.
• Found that LCN2, another overexpressed gene in BLCA, interacts with captopril-associated proteins.
• Molecular docking revealed specific amino acid residues in MMP9 and LCN2 that interact with captopril.

Conclusions:

• Captopril demonstrates significant inhibitory potential against human MMP9 and LCN2 proteins, crucial in BLCA.
• These findings support further in vitro and in vivo studies to assess captopril's efficacy in treating BLCA.
• Captopril could be a potential treatment for BLCA patients with elevated MMP9 and LCN2 expression, irrespective of hypertension.