Sitotoksisitas Ekstrak Etanolik Benalu batu (Begonia medicinalis Ardi & D.C. Thomas) Asal Sulawesi Tengah Terhadap Sel Kanker Paru-paru A549

Ni Kadek Dewi Permatasari, Prof. Dr. Rarastoeti Pratiwi, M.Sc.

2025 | Tesis | S2 Biologi

Kanker paru-paru salah satu penyebab utama kematian akibat kanker di dunia. Terapi standar seperti cisplatin sering digunakan, tetapi penggunaannya dalam jangka panjang memberi efek toksik terhadap sel normal. Oleh karena itu, pencarian terapi alternatif berbasis herbal semakin menarik perhatian. Salah satu kandidat potensial adalah Benalu batu (Begonia medicinalis), tanaman endemik sulawesi yang telah lama digunakan sebagai obat tradisional, termasuk untuk pengobatan tumor dan kanker. Penelitian ini bertujuan untuk mengevaluasi potensi antikanker ekstrak etanolik Benalu batu secara in vitro terhadap sel kanker paru-paru A549 dan sel Vero, serta secara in silico terhadap protein EGFR-TK dan Bcl2, yang masing-masing berperan dalam proliferasi dan penghambatan apoptosis kanker paru-paru tipe NSCLC. Uji sitotoksisitas menggunakan MTT assay, kromatografi lapis tipis (KLT) digunakan untuk memantau profil senyawa dalam ekstrak, sedangkan identifikasi senyawa menggunakan GC-MS. Evaluasi kelayakkan farmakokinetik senyawa dilakukan melalui analisis Lipinski”s rule of five menggunakan SwissADME, dan studi molecular docking menggunakan Pyrx serta discovery studio. Hasil penelitian menunjukkan bahwa ekstrak etanolik Benalu batu liar memiliki potensi sitotoksik lebih tinggi terhadap sel A549 dibandingkan ekstrak dari tanaman budidaya, dengan nilai IC?? sebesar 134,71 µg/mL dan tidak bersifat toksik terhadap sel Vero (IC?? sebesar 517,24 µg/mL). Analisis profil kromatogram menunjukkan bahwa senyawa dalam ekstrak Benalu batu liar cenderung bersifat non-polar. Uji sitotoksisitas fraksi potensial dari ekstrak Benalu batu liar menunjukkan Fraksi A paling potensial dengan nilai IC?? 33,93 µg/mL dan memiliki selektivitas tinggi terhadap sel kanker dengan nilai IS sebesar 24,52. Analisis GC-MS mengidentifikasi delapan senyawa bioaktif yang diduga memiliki aktivitas antikanker. Studi molecular docking terhadap protein EGFR-TK menunjukkan bahwa senyawa campesterol (-9,2 kcal/mol), stigmasterol (-9,1 kcal/mol), dan sitosterol (-8,2 kcal/mol) memiliki afinitas pengikatan yang lebih tinggi dibandingkan kontrol (gefitinib, -7,7 kcal/mol). Pada protein Bcl-2, sitosterol menunjukkan afinitas terkuat (-8,7 kcal/mol), diikuti oleh squalene dan stigmasterol (-8,5 kcal/mol), serta campesterol (-8,4 kcal/mol).

Lung cancer is one of the leading causes of cancer-related deaths worldwide. Standard therapies such as cisplatin are commonly used; however, long-term use often results in toxic effects on normal cells. Therefore, the search for alternative herbal-based therapies has gained increasing attention. One potential candidate is Benalu batu (Begonia medicinalis), an endemic plant of Sulawesi that has long been used in traditional medicine, including for the treatment of tumors and cancer. This study aims to evaluate the anticancer potential of ethanolic extract of Benalu batu in vitro against A549 lung cancer cells and Vero cells, as well as in silico against EGFR-TK and Bcl-2 proteins, which play roles in proliferation and inhibition of apoptosis in non-small cell lung cancer (NSCLC). Cytotoxicity was assessed using the MTT assay, thin-layer chromatography (TLC) was employed to monitor the compound profile in the extract, and compound identification was conducted using GC-MS. Pharmacokinetic feasibility was evaluated based on Lipinski’s Rule of Five using SwissADME, and molecular docking studies were carried out using PyRx and Discovery Studio. The results showed that the ethanolic extract of wild Benalu batu exhibited higher cytotoxic potential against A549 cells compared to cultivated plant extract, with an IC?? value of 134.71 µg/mL, and was non-toxic to Vero cells (IC?? value of 517.24 µg/mL). Chromatographic profile analysis indicated that compounds in the wild Benalu batu extract tend to be non-polar. Cytotoxicity testing of potential fractions revealed that Fraction A had the strongest activity, with an IC?? value of 33.93 µg/mL and high selectivity toward cancer cells, with a selectivity index (SI) of 24.52. GC-MS analysis identified eight bioactive compounds suspected to possess anticancer activity. Molecular docking studies against EGFR-TK protein showed that campesterol (-9.2 kcal/mol), stigmasterol (-9.1 kcal/mol), and sitosterol (-8.2 kcal/mol) had higher binding affinities compared to the control (gefitinib, -7.7 kcal/mol). For the Bcl-2 protein, sitosterol demonstrated the strongest binding affinity (-8.7 kcal/mol), followed by squalene and stigmasterol (-8.5 kcal/mol), and campesterol (-8.4 kcal/mol).

Kata Kunci : Begonia medicinalis, Sel A549, Sel Vero, Sitotoksisitas, GC-MS, Molecular Docking, Begonia medicinalis, A549 cells, Vero cells, Cytotoxicity, GC-MS, Molecular Docking