Document Type : Research Articles
Authors
1
Department of Oral Pathology, Saveetha Dental College and Hospital,Saveetha Institute of Medical and Technical Sciences,Saveetha University, Poonamallee High Road, Velappanchavadi, Chennai, India.
2
Department of Oral and Maxillofacial Pathology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
Abstract
Background: Oral squamous cell carcinoma (OSCC) remains a significant health burden with limited therapeutic options and high mortality. Sesbania grandiflora, a medicinal plant rich in phytochemicals, has been traditionally used for its medicinal properties and is emerging as a potential anticancer agent. Objective: This study aimed to investigate the anticancer mechanisms of S. grandiflora against OSCC using an integrated approach, combining network pharmacology, molecular docking, ADME profiling, and in vitro validation. Materials and Methods: Network pharmacology was employed to identify hub genes and pathways associated with S. grandiflora bioactives. Molecular docking was performed to evaluate binding interactions of D-glucuronic acid, a major phytoconstituent, with key cancer-related targets. ADME profiling assessed drug-likeness and pharmacokinetic properties. in vitro assays, including MTT, flow cytometry, and Western blotting, were conducted on KB oral cancer cells to validate mechanistic insights. Results: Key hub genes identified included AKT1, BCL2, PIK3CA, MTOR, and CASP8, which were enriched in pathways such as the PI3K–Akt, p53, HIF-1, and EGFR-mediated apoptosis pathways. Molecular docking revealed strong and stable interactions of D-glucuronic acid with target proteins, supporting its multi-targeted activity. ADME analysis indicated favorable pharmacokinetic properties, including high GI absorption, BBB permeability, and minimal CYP450 inhibition. Experimental validation demonstrated significant cytotoxicity (IC₅₀: 250–300 µg/mL), dose-dependent G1-phase cell cycle arrest, downregulation of BCL-2, and upregulation of BAX, confirming the induction of apoptosis. Conclusion: S. grandiflora exerts anticancer effects through modulation of PI3K-AKT-mTOR and apoptotic pathways. D-glucuronic acid emerges as a promising bioactive compound, supporting further in vivo studies and clinical exploration for OSCC management.
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