Quinoxaline from Marine Mangrove (Rhizophora apiculata) Exhibits Anti-Metastatic Potential against B16F-10 Melanoma Cells in In-Vitro and In-Vivo Models

Abstract

Background: Lung cancer remains the leading cause of cancer related mortality worldwide, with non-small cell lung carcinoma (NSCLC) representing the most prevalent and aggressive subtype due to its high metastatic potential. Despite therapeutic advances, current treatment options are often insufficient, underscoring the need for novel anti-metastatic strategies.

Objective: This study investigates the anti-metastatic potential of a quinoxaline in a B16F-10melanoma-induced experimental lung metastasis model in BALB/c mice.

Methods: Mice were administered quinoxaline (10 mg/kg body weight, intraperitoneally), and its effects on lung metastasis, survival, biochemical markers and matrix metalloproteinases (MMPs) were assessed. Molecular docking studies were also performed to evaluate the compound’s interaction with MMP-2 and MMP-9.

Results: Quinoxaline treatment resulted in a significant reduction (p < 0.01) in the number of lung metastatic nodules and enhanced survival rates in treated mice. The compound effectively restored the levels of metastatic biomarkers, including hydroxyproline, uronic acid, hexosamine, gamma-glutamyl transpeptidase (GGT), nitric oxide (NO) and sialic acid, towards normal physiological ranges. Molecular docking studies further revealed strong inhibitory interactions of quinoxaline with MMP-2 and MMP-9, supporting its role in suppressing extracellular matrix degradation and tumor cell invasion.

Conclusion: Our findings demonstrate that quinoxaline exhibits potent anti-metastatic activity by modulating metastatic biomarkers and inhibiting MMP activity, suggesting its potential as a promising therapeutic agent for the management of lung cancer metastasis.