Background: Urolithins are bioactive metabolites that arise from the metabolism of ellagic acid, a polyphenolic compound found abundantly in various fruits, particularly berries, and nuts. Upon ingestion, ellagic acid undergoes transformation by the gut microbiota through processes such as decarboxylation and dehydroxylation, resulting in the formation of several urolithins, with urolithin A (UroA) being one of the most studied due to its promising pharmacological properties. UroA has garnered attention for its diverse health benefits, including antimicrobial, antioxidant, neuroprotective, and anti-inflammatory effects. These properties suggest that UroA may play a significant role in mitigating various diseases, including cancer. In particular, lung squamous cell carcinoma (LSCC), a subtype of non-small cell lung cancer (NSCLC), is characterized by aggressive behavior and a high propensity for metastasis. Matrix metalloproteinases (MMPs), especially MMP-9, are zinc-dependent endopeptidases that are crucial for extracellular matrix (ECM) remodeling. Objective: Urolithins are bioactive compounds derived from ellagic acid found in berries and nuts. Following ingestion, the gut microbiota metabolizes ellagic acid through decarboxylation and dehydroxylation, producing various urolithins, including urolithin A (UroA). A range of pharmaceutical properties has been introduced for UroA, including antimicrobial, antioxidant, neuroprotective, and anti-inflammatory effects. Matrix metalloproteinases (MMPs), particularly MMP-9, are zinc-dependent endopeptidases that play a crucial role in extracellular matrix remodeling, thereby facilitating cancer metastasis. This study aimed to explore the potential of UroA to target MMP9 in lung squamous cell carcinoma. Methods: The expression of MMP-9 was analyzed in lung squamous cell carcinoma tissues compared to normal samples using online tools. The Proteins Plus web server was employed for molecular docking to assess the binding affinity of UroA with the active site of MMP-9. Results: Gene expression analysis using UALCAN revealed a significant upregulation of MMP-9 in lung squamous cell carcinoma samples (n=503) compared to normal specimens (n=52), with a p-value of 1.11E-16. Molecular docking results indicated a favorable interaction between UroA and MMP-9, with two hydrogen bonds formed with Gln402 and Ala191, pi-pi bonds with His411 and His405, along with van der Waals interactions with His411, His405, and Phe110, all located in the cofactor binding site of MMP-9, yielding a -1.63 JAMDA score. Conclusion: Present study identified MMP-9 as a promising target for combating metastasis in lung squamous cell carcinoma. The molecular docking results suggest a po

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