In Vitro and In Silico Study of the Anticancer Activity of Benalu batu (Begonia medicinalis Ardi & D.C. Thomas) an Endemic Plant of Sulawesi Against A549 Lung Cancer Cells
DOI:
https://doi.org/10.11113/mjfas.v22n3.4699Keywords:
Begonia medicinalis, anticancer, GC-MS, A549 cells, molecular docking.Abstract
Lung cancer is one the leading causes of cancer related deaths worldwide. Standard therapies such as cisplatin are commonly used however, their long-term use can lead toxic effects on normal cells. Consequently, the search for alternative herbal based therapies has gained increasing attention. One potential candidate is Benalu batu (Begonia medicinalis), an endemic plant from Sulawesi that has been traditionally used as remedy for various ailments, including tumors and cancer. This study aims to evaluate the anticancer potential of ethanolic extract and fraction of Benalu batu both in vitro A549 lung cancer cells and Vero cells, and in silico against EGFR-TK and Bcl-2 proteins, which are involved in the progression of Non-Small Cell Lung Cancer (NSCLC). Cytotoxicity was assessed using the MTT assay, while compound identification was performed using Thin Layer Chromatography (TLC) and Gas Chromatography-Mass Spectrometry (GC-MS). Druglikeness feasibility was evaluated through Lipinski’s Rule of Five using SwissADME, and molecular docking studies were conducted using PyRx and Visualized with Discovery Studio. The results demonstrated that the ethanolic extract of wild Benalu batu exhibited higher cytotoxic activity compared to the cultivated plant extract, with an IC50 value of 134.71 µg/mL, and was nontoxic to Vero cells (IC50 = 517.24 µg/mL). Thin Layer Chromatography profiling indicated that the compounds in the wild Benalu batu extract are predominantly non-polar. Cytotoxicity testing of the active fractions revealed that fraction A exhibited the most potent activity with an IC50 of 33.93 µg/mL and high selectivity index of 24.52, surpassing that of cisplatin. Gas Chromatography-Mass Spectrometry analysis identified eight bioactive compounds suspected to have anticancer potential, these compounds are stigmasterol (19.80%), campesterol (7.06%), neophytadiene (4.83%), sitosterol (3.29%), squalene (2.73%), phytol (2.39%), phytol acetate (1.22%), hexadecenoic acid ethyl ester (1.22%), and α-tocopheryl acetate (1.10%). Molecular docking against the EGFR-TK protein showed that campesterol (-9.2 kcal/mol), stigmasterol ((-9.1 kcal/mol), and sitosterol (-8.2 kcal/mol), had more favorable binding affinity values compared to the control drug gefitinib (-7.7 kcal/mol). Sitosterol exhibited the highest binding affinity
(-8.7 kcal/mol) against Bcl-2 protein, followed by squalene and stigmasterol (-8.5 kcal/mol), and campesterol (-8.4 kcal/mol).
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