Phytochemical Characterisation and In Vitro Anticancer Potential of Combretum indicum Leaf Aqueous Extract Against A549 Cells
TL;DR
The aqueous leaf extract of C. indicum demonstrated promising antioxidant and anti-cancer potential and stigmasterol emerged as the most promising lead phytoconstituent against EGFR, ALK, ROS1, PI3K, and MET.
Abstract
Background: Lung cancer is a major cause of cancer-related morbidity and mortality worldwide. Plant-derived therapeutics have attracted attention as safer, multitarget candidates for cancer management. Aim: This study evaluated the phytochemical profile, antioxidant activity, selective cytotoxicity, and docking-based anti-cancer potential of the aqueous leaf extract of Combretum indicum in A549 cells. Methods: Qualitative and quantitative phytochemical analyses were performed, followed by antioxidant assays [2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide, nitric oxide, lipid peroxidation, and Ferric Reducing Antioxidant Power (FRAP)], Gas Chromatography-Mass Spectrometry (GC-MS), 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assays in A549 and Vero cells, and molecular docking against Epidermal Growth Factor Receptor (EGFR), Anaplastic Lymphoma Kinase (ALK), C-Ros Oncogene 1 Receptor Tyrosine Kinase (ROS1), Phosphatidylinositol 3-Kinase (PI3K), and Mesenchymal-Epithelial Transition Receptor (MET). Results: The extract contained alkaloids, flavonoids, tannins, carbohydrates, proteins, and sterols. Flavonoids and tannins were present at high levels. C. indicum-Aqueous Leaf Extract (CI-ALE) showed concentration-dependent antioxidant activity and selective cytotoxicity against A549 cells, with an IC50 of 163.11 µg/mL. More than 80% of Vero cells remained viable at the highest tested concentration. GC-MS detected 38 compounds; phytol, n-hexadecanoic acid, octahydro-2(1H)-quinoline, and stigmasterol were prominent. Docking analysis showed that stigmasterol had the strongest binding affinity across major non-small cell lung cancer targets. Conclusion: The aqueous leaf extract of C. indicum demonstrated promising antioxidant and anti-cancer potential. Further mechanistic and in vivo evaluation is warranted. Major Findings: CI-ALE showed selective cytotoxicity toward A549 cells, strong antioxidant activity, and multi-target docking interactions. Stigmasterol emerged as the most promising lead phytoconstituent against EGFR, ALK, ROS1, PI3K, and MET.